Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Short description of key information:

In accordance with column 2 of REACH Annex VIII, the screening for reproductive/developmental toxicity study (required in section 8.7.1) does not need to be conducted as a pre-natal developmental toxicity study in rat is available.

Developmental toxicity is being addressed with a Testing Proposal for an OECD TG 443 study.

Effects on developmental toxicity

Description of key information

A GLP prenatal development toxicity study on isopropyl chloride (IPC) in rats conducted according to OECD guideline 414 indicated that the inhalational NOAEC for developmental toxicity was 6.67 mg/L (6670 mg/m^3), the highest dose administered.  A NOAEC for maternal toxicity was not identified by the study author; however, a review of the data indicate that a NOAEC of 1.43 mg/L (1430 mg/m^3) can be considered for maternal effects.

Effect on developmental toxicity: via inhalation route
Dose descriptor:
6 670 mg/m³
Additional information

The effect of isopropyl chloride (IPC) on embryofetal development was evaluated in a GLP-compliant prenatal development toxicity study that was conducted according to OECD test guideline 414 (LPT Laboratory, 1992). IPC was administered by whole body inhalation to timed-pregnant Sprague-Dawley rats at dose concentrations of 0 (sham exposed), 0.61, 1.43, 2.66, or 6.67 mg/L (actual concentrations) for 6 hours/day, from gestational days 6 through 15. There were no mortalities reported. There were no maternal findings reported at the 0.61 and 1.43 mg/L dose levels. There were no changes in maternal body weight or food and drinking water consumption reported. Gross macroscopic inspection showed dark-red foci in the lungs of 2 of 20 dams in approximately 5% to 10% of the pulmonary tissue at the 2.66 mg/L dose concentration. At the 6.67 mg/L dose concentration, dark red, partly indurated foci in the lungs were reported in 9 out of 20 dams. These lesions occupied approximately 5% to 50% of the pulmonary tissue. Multiple beige foci also were detected in 8 of 20 dams. There were no discernable effects on embryotoxicity or fetotoxicity parameters at any dose level tested. At the highest IPC concentration, an increase in fetal variations consisting of slightly delayed ossification of the skull and vertebrae was reported. While this increase could be explained by maternal toxicity and/or biological variability, a relationship to the test article could not be excluded. It was concluded that there were no teratogenic effects observed. Based on these findings, the NOAEC for developmental toxicity was considered to be 6.67 mg/L (6670 mg/m3), the highest dose administered. While the study author did not identify a NOAEC for maternal toxicity, a review of the data indicates that a NOAEC of 1.43 mg/L (1430 mg/m3) can be considered for maternal toxicity.

Justification for classification or non-classification

The developmental study indicated that the submission substance does not affect the development of the offspring. However, no information is available on reproductive toxicity. As a result, data is lacking for classification according to Regulation (EC) No 1272/2008, Annex I section 3.7.