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EC number: 947-870-6 | CAS number: -
Sustained decreased body weights, body weight gain in repeated dose oral study of the amine in rats
The draft EU Risk Assessment Report (2008) states the NOAEL for the category of primary (fatty) alkylamines is 3.25 mg/kg bw/day, based on body weight changes after 28 days oral gavage to octadec-9-enylamine. The expert committee stated that this guideline study (under GLP) is adequate for filling the data gaps of the category and no additional repeated dose toxicity is needed. The NOAEL of 3.25 mg/kg bw/d is used for determination of the DNEL of the registered substance.
A risk assessment has been undertaken for a metabolite, terephthalic acid (TPA). This risk assessment includes TPA and its esters, namely dimethyl phthalate (DMT) and diethylhexyl phthalate (DEHP) (Ball GL, McLellan CJ and Bhat VS, 2012. Toxicological review and oral risk assessment of terephalic acid (TPA) and its ester: A category approach. Crit Review Toxicol 42(1): 28-67). Experimental data from published and unpublished toxicity and toxicokinetic studies were reviewed. The critical effect of TPA was determined to be urinary bladder urolith formation with secondary transitional cell tumor development. This was confirmed by the authors as a threshold effect, and a critical concentration of 8 mM TPA in urine has been calculated as required to achieve saturation of human urine with calcium terephthalate; this corresponds to approximately 2000 mg/kg bw/d in humans (Heck, 1981). The NOAEL for TPA in a 2012 risk assessment is 142 mg/kg bw/d based on the key CIIT 1993 chronic study. The findings of studies on the other TPA esters were consistent; the BMDL10 from a 1979 NTP chronic study on DMT was 148 mg/kg bw/d based on kidney inflammation in female rats, and the BMDL10 from a chronic study on DEHP (Deyo, 2008) was 54 mg/kg bw/d based on retinal effects in female rats. The uncertainty factors (assessment factors) applied in this risk assessment were 10 for interspecies, 10 for intraspecies, 1 for dose-response (LOAEL to NOAEL), 1 for duration of study, and 3 for uncertainties associated with database deficiencies. For TPA, the point of departure (oral reference dose (RfD)) was 0.5 mg/kg bw/d; consistent with 0.5 mg/kg bw/d for DMT and 0.2 mg/kg bw/d for DEHP (appropriate considering the higher molecular weight of the larger ester). With exposure input, the total allowable concentration (TAC) of TPA in drinking water is 3 mg/L (rounded). TPA is listed in Annex I of Food Contact Materials (EC, 2009) with a specific migration limit of 7.5 mg/kg food; it is also listed in the US 21 CFR as acceptable for food contact use in resinous and polymeric coatings.
Male and female rats were exposed to terephalic acid vapour for 6 hours per day, for 28 days. There were no significant findings in any systemic toxicity endpoint, and only minimal local tracheal epithelial degeneration was observed at the high dose of 3.3 mg/m3. The NOAEC for TPA was considered 3.3 mg/m3.
The oral/dermal and inhalation values for the points of departure for TPA are higher than those for the amines; therefore, the NOAEL for amines is used as the point of departure for risk assessment for the registered substance.
In repeated dose studies of the potentially bioavailable metabolites of the registered substance, there was no evidence of specific target organ toxicity after repeated dose exposure. The substance does not meet the criteria for STOT-RE according to Regulation EC No. 1272/2008.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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