Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Data on ortho-Diaminotoluene, propoxylated, were used, a read-across candidate. Using this substance in reproduction toxicity screening study (oral gavage) following the OECD guideline 421, a NOAEL (reproductive toxicity): = 160 mg/kg bw was elicited.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
160 mg/kg bw/day
Study duration:
subacute
Species:
rat
Additional information

Read across justification

A reproductive toxicity study is not available on the substance Oligomeric reaction product of formaldehyde, aniline and 2-methyloxirane, and reaction product of 2,2'-oxydiethanol and 2-methyloxirane (EC917-215-9) (target substance), therefore data has been used from 1,2-Diaminotoluene, propoxylated (CAS 1228577-90-9) (analogue substance 2) to address this data gap.

See section 13 for the read-across justification report.

 

Target substance:

Based on available toxicological data, the target substance has a low order of toxicity (LD50 > 2000 mg/kg), is not irritating to eye or skin and has a low potential for genotoxicity. The target substance is a dermal sensitiser.

 

Analogue 2 substance:

Analogue substance 2 (CAS 1228577-90-9) has a low order of toxicity (LD50 > 2000 mg/kg), is not irritating to eye or skin, is not a dermal sensitiser, has a low potential for genotoxicity and is not toxic to reproduction or development.

 

Reproductive toxicity data:

Analogue substance 2 was evaluated in a reproductive and developmental screening protocol (OECD 421) in rats. Dosing levels tested were 0, 10, 40 and 160 mg/kg/d. Decreases in food consumption and body weights were observed in the high dose group dams. No effects were observed on mating behaviour, fertility, insemination and live birth indices, gestation parameters, number of implantation sites or prenatal loss, litter size, number of pups born, viability of pups and pup weight up to the 160 mg/kg dose group. The NOAEL on reproduction was 160 mg/kg/day.  

There is a slight bias anticipated in using the analogue 2 substance as a read-across to predicting effects of the target substance. Analogue 2 is likely to be more bioavailable after oral administration than the target substance – see section 3.4.1. This increase in potential bioavailability for the analogue substance would make it worst-case with respect to the target substance. Thus, the results from the analogue substance have the potential to over-predict the effects of the target substance when based on administered dose. 

Conclusion

The available data demonstrates a pattern of similar and limited toxicological properties across the target and analogue substances. It is postulated that any differences observed may be accounted for by the increased surfactant activity of the target substance. 

Therefore, it is concluded that read across is appropriate and reproductive / development toxicological data can be used from analogue 2 to the target substance.


Effects on developmental toxicity

Description of key information

1,2-Diaminotoluene, propoxylated (CAS 1228577-90-9) (analogue substance 2)was evaluated in a reproductive and developmental screening protocol (OECD 421) in rats. Dosing levels tested were 0, 10, 40 and 160 mg/kg/d. Decreases in food consumption and body weights were observed in the high dose group dams. There were no remarkable clinical or necropsy findings in pups and no adverse effects on the course of birth or lactation behaviour of the dams in these groups. The NOAEL on developmental effects was 160 mg/kg/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
160 mg/kg bw/day
Study duration:
subacute
Species:
rat
Additional information

Read across justification

A developmental toxicity study is not available on the substance Oligomeric reaction product of formaldehyde, aniline and 2-methyloxirane, and reaction product of 2,2'-oxydiethanol and 2-methyloxirane (EC917-215-9) (target substance), therefore data has been used from 1,2-Diaminotoluene, propoxylated (CAS 1228577-90-9) (analogue substance 2) to address this data gap.

 

Target substance:

Based on toxicological available, the target substance has a low order of toxicity (LD50 > 2000 mg/kg), is not irritating to eye or skin and has a low potential for genotoxicity. The target substance is a dermal sensitiser.

 

Analogue 2 substance:

Analogue substance 2 (CAS 1228577-90-9) has a low order of toxicity (LD50 > 2000 mg/kg), is not irritating to eye or skin, is not a dermal sensitiser, has a low potential for genotoxicity and is not toxic to reproduction or development.

 

Developmental toxicity data:

Analogue substance 2 was evaluated in a reproductive and developmental screening protocol (OECD 421) in rats. Dosing levels tested were 0, 10, 40 and 160 mg/kg/d. Decreases in food consumption and body weights were observed in the high dose group dams. There were no remarkable clinical or necropsy findings in pups and no adverse effects on the course of birth or lactation behaviour of the dams in these groups. The NOAEL on developmental effects was 160 mg/kg/day.

There is a slight bias anticipated in using the analogue 2 substance as a read-across to predicting effects of the target substance. Analogue 2 is likely to be more bioavailable after oral administration than the target substance – see section 3.4.1. This increase in potential bioavailability for the analogue substance would make it worst-case with respect to the target substance. Thus, the results from the analogue substance have the potential to over-predict the effects of the target substance when based on administered dose. 

Conclusion

The available data demonstrates a pattern of similar and limited toxicological properties across the target and analogue substances. It is postulated that any differences observed may be accounted for by the increased surfactant activity of the target substance. 

Therefore, it is concluded that read across is appropriate and reproductive / developmental toxicological data can be used from analogue 2 to the target substance.

Justification for classification or non-classification

The findings in the available study do not warrant classification according to the EU criteria.