Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No other concerns identified.
Additional information

Reproductive and developmental toxicity studies were not located for the submission substance (CASRN 70225-05-7). However, data from the chemical category Trimellitates are available and was used as read-across for the sake of hazard assessment. 

 

The OECD reproductive/developmental toxicity screening test [TG 421] on a structurally analogous trimellitate ester, TOTM, at doses of 100, 300 and 1,000 mg/kg/day in rats demonstrated a decrease of spermatocytes and spermatids in testis in the 300 and 1000 mg/kg groups but not in the 100 mg/kg group. The lack of physiologic impact on male reproduction capacity suggests this finding is not indicative of an adverse effect.  No adverse effects on copulation, fertility, delivery, nursing or histopathology of females nor on the viability, body weight and morphology of offspring. Based on the testicular effects, the NOAEL for repeated dose toxicity is considered to be 100 mg/kg bw/day. NOAELs for reproductive toxicity in females and developmental toxicity of offspring were considered to be 1,000 mg/kg bw/day.

These data together with the likely limited bioavailability of the submission substance (as described in the toxicokinetic assessment, IUCLID section 7.1) are considered adequate to conclude the submission substance has a low potential for developmental/reproductive toxicity. This is consistent with the recent SIDS evaluation that concluded the hazards of trimellitate esters towards human health are considered to be low and that the existing data are adequate to make this assessment (US EPA, 2009). 

Justification for Read-Across

The Trimellitate Category-as defined in the US Environmental Protection Agency’s (EPA) High Production Volume (HPV) Challenge Program and the Organization for Economic Cooperation and Development’s (OECD) Screening Initial Data Set (SIDS)-, includes four chemicals containing individual trimellitate triesters or mixed trimellitate esters, which are defined as esters of 1,2,4,-benzenetricarboxylic acids that have branched or branched and linear alkyl groups. The members are: 1,2,4-benzenetricarboxylic acid, tris (2-ethylhexyl) ester (CASRN 3319-31-1 [TOTM]); 1.2.4-benzenetricarboxylic acid, triisooctyl ester (CASRN 27251-75-8 [TIOTM]); 1,2,4-benzenetricarboxylic acid, triisononyl ester (CASRN 53894-238 [TINTM]); and 1,2,4-benzenetricarboxylic acid, decyl octyl ester (CASRN 67989-23-5 [DOTM]).  The Trimellitate Category was formed on the principle that substances of similar structure have similar toxicological properties and the premise that a narrow range of ester carbon numbers will produce trends in physicochemical, environmental and toxicological properties.

 

The submission substance (CASRN 70225-05-7) fits the Trimellitate Category definition of an ester of 1,2,4-benzenetricarboxylic acid with branched and linear alkyl groups, with the distinction of having side chains of slightly longer length (C10, and C13). Because of the similarity in structure and physicochemical properties, it is reasonable to rely on theavailable data on the HPV Trimellitate substances to characterize the human health effects of CSRN 70255-05-7 (see read-across justification in section 13 of IUCLID dossier for more information).


Short description of key information:
One Key Study, read-across- Not expected to cause reproductive toxicity (OECD 421)

Effects on developmental toxicity

Description of key information
One supporting study. Not expected to cause developmental toxicity based on available science
Additional information

Taking into account the results of all of the available test data provided in this dossier, the physicochemical properties of trimelletate esters, and with respect to animal welfare, the conduction of a developmental toxicity study is scientifically not justified as it is unlikely to yield any additional indication of risk. The available data are adequate for risk assessment and therefore no further testing are proposed.

Justification for classification or non-classification

The available data are considered adequate to conclude that classification is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP), under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations, or under the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).