From: Peter Zavon <pzavon**At_Symbol_Here**>
Subject: Re: [DCHAS-L] Limonene article in CEN
Date: Tue, 19 Mar 2019 10:58:01 -0400
Reply-To: ACS Division of Chemical Health and Safety <DCHAS-L**At_Symbol_Here**PRINCETON.EDU>
Message-ID: 007001d4de64$27aa8710$76ff9530$**At_Symbol_Here**
In-Reply-To <48505608.6189415.1552926055528**At_Symbol_Here**>

The orange juice industry is so efficient at removing the orange rind before squeezing the pulp for juice that they have to add d-limonene BACK into the juice before packaging. If they don't, it does not taste like orange juice.


I learned about this ore than 20m years ago, when my then employer was using a d-limonene solution in water in a spray degreasing operation. The operators wore slickers and face masks, and called the stuff being sprayed "orange juice" because of the odor.



Peter Zavon, CIH
Penfield, NY




-----Original Message-----


From: ACS Division of Chemical Health and Safety [mailto:DCHAS-L**At_Symbol_Here**PRINCETON.EDU] On Behalf Of Monona Rossol
Sent: Monday, March 18, 2019 12:21 PM
Subject: Re: [DCHAS-L] Limonene article in CEN




D-Limonene is a Category 1 skin sensitizer and it has NO BUSINESS in cosmetics. I predict in a few more years there will be sufficient human data to associate it with asthma.   The reason it is in all our products is that we drink a lot of orange juice which means there are tons of this smelly stuff that need a market.


Let's hope d-limonene finds it's true market as just a pesticide/repellant/biocide under EPA rules.






from: ACS Division of Chemical Health and Safety <DCHAS-L**At_Symbol_Here**PRINCETON.EDU> on behalf of TILAK CHANDRA <0000058f112ac338-dmarc-request**At_Symbol_Here**LISTS.PRINCETON.EDU>
Sent: Monday, March 18, 2019 8:30 AM
Subject: Re: [DCHAS-L] Limonene article in CEN


FYI. Tilak
From literature:

R-(+)-limonene (D-limonene) is a commonly used flavor additive in food, beverages and fragrances for its pleasant lemon-like odor.  Considering its increasing applications, it's necessary to understand toxicol. effects and risk assocd. with its use.  R-(+)-limonene is rapidly absorbed in exptl. animals and human beings following oral administration.  In humans, it gets distributed to liver, kidney, and blood resulting in the formation of metabolites like perillic acid, dihydroperillic acid, limonene-1,8-diol and limonene-1,2 diol.  Important toxic effects primarily reported in rodents are severe hyaline droplet nephrotoxicity (only in male rats due to specific protein =CE=B12u-globulin; however, this effect isn't valid for humans), hepatotoxicity and neurotoxicity.  R-(+)-limonene does not show genotoxic, immunotoxic and carcinogenic effects.  Substantial data is available about limonene's stability after treatment with thermal and non-thermal food processing techniques; however!
 , information about toxicity of metabolites formed and their safe scientific limits is not available.  In addn., toxicity of limonene degrdn. products formed during storage of citrus juices isn't known.  Based on all available toxicol. considerations,

R-(+)-limonene can be categorized as low toxic additive.  More detailed studies are required to better understand interaction of limonene with modern food processing techniques as well as degrdn. products generated and toxicity arising from such products.
A review.  Limonene was one of the main ingredients in citrus essential oils.  It had been widely used in food and pharmaceutical industries due to its antibacterial and anticancer bioactivities.  This paper reviewed recent progress in understanding the safety of limonene from the perspectives of toxicol. assessment, genotoxicity, cytotoxicity and its influence on human, animals and environment.  We hoped that this review could provide refs. for the effective and safe application of limonene.
By: Kim, Young Woo; Kim, Min Ji; Chung, Bu Young; Bang, Du Yeon; Lim, Seong Kwang; Choi, Seul Min; Lim, Duck Soo; Cho, Myung Chan; Yoon, Kyungsil; Kim, Hyung Sik; Kim, Kyu Bong; Kim, You Sun; Kwack, Seung Jun; Lee, Byung-Mu
A review.  D-Limonene, a major constituent of citrus oils, is a monoterpene widely used as a flavor/fragrance additive in cosmetics, foods, and industrial solvents as it possesses a pleasant lemon-like odor.  D-Limonene has been designated as a chem. with low toxicity based upon LD (LD50) and repeated-dose toxicity studies when administered orally to animals.  However, skin irritation or sensitizing potential was reported following widespread use of this agent in various consumer products.  In exptl. animals and humans, oxidn. products or metabolites of D-limonene were shown to act as skin irritants.  Carcinogenic effects have also been obsd. in male rats, but the mode of action (MOA) is considered irrelevant for humans as the protein =CE=B12u-globulin responsible for this effect in rodents is absent in humans.  Thus, the liver was identified as a crit. target organ following oral administration of D-limonene.  Other than the adverse dermal effects noted in humans, other notable!
  toxic effects of D-limonene have not been reported.  The ref. dose (RfD), the no-obsd.-adverse-effect level (NOAEL), and the systemic exposure dose (SED) were detd. and found to be 2.5 mg/kg/d, 250 mg/kg//d, and 1.48 mg/kg/d, resp.  Consequently, the margin of exposure (MOE = NOAEL/SED) of 169 was derived based upon the data, and the hazard index (HI = SED/RfD) for D-limonene is 0.592.  Taking into consideration conservative estn., D-limonene appears to exert no serious risk for human exposure.  Based on adverse effects and risk assessments, D-limonene may be regarded as a safe ingredient.  However, the potential occurrence of skin irritation necessitates regulation of this chem. as an ingredient in cosmetics.  In conclusion, the use of D-limonene in cosmetics is safe under the current regulatory guidelines for cosmetics.

D-limonene is one of the most common terpenes in nature.  It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit).  D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding.  D-limonene is considered to have fairly low toxicity.  It has been tested for carcinogenicity in mice and rats.  Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor.  Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans.  In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year.  Being a solvent of cholesterol, d-limonene has!
  been used clinically to dissolve cholesterol-containing gallstones.  Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD).  D-limonene has well-established chemopreventive activity against many types of cancer.  Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.

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