Registration Dossier

Administrative data

Description of key information

A 28 days repeated dose oral toxicity study conducted with a member of the chemical category similar to OECD 407 was considered appropriate to determine the repeated oral toxicity of the substance. The NOAEL was determined to be 92.5 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
In Section 13 of the IUCLID dossier, a report is attached in which the category approach is reported according to ECHA Guidance for the implementation of REACH, Guidance on information requirements and chemical safety assessment, Chapter R.6 (reporting format for a chemical category).
Reason / purpose:
read-across source
Key result
Dose descriptor:
LOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
organ weights and organ / body weight ratios
Key result
Dose descriptor:
LOAEL
Effect level:
185 mg/kg bw/day (actual dose received)
Based on:
other: solid content of test material
Sex:
female
Basis for effect level:
other: The solid content of the testmaterial is 37%. The LOAEL based on the testmaterial is 500 mg/kg bw/day. Calculation: 500 x 0.37 = 185 mg/kg bw/day (LOAEL based on the solid content of the substance)
Key result
Dose descriptor:
NOAEL
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
organ weights and organ / body weight ratios
Key result
Dose descriptor:
NOAEL
Effect level:
92.5 other: mg/kg bw/day (actual dose received of the solid content of the substance)
Based on:
other: solid content of test material
Sex:
female
Basis for effect level:
other: The solid content of the testmaterial is 37%. The NOAEL based on the testmaterial is 250 mg/kg bw/day. Calculation: 250 x 0.37 = 92.5 mg/kg bw/day (NOAEL based on the solid content of the substance)
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
500 mg/kg bw/day (actual dose received)
System:
hepatobiliary
Organ:
liver
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified
Conclusions:
A 28 days repeated dose oral toxicity study was conducted with Dehyton G (an aqueous solution of Amphoacetates C8-C18) similar to OECD 407. Based on a dose-dependent effect on liver weight in females the NOAEL for the testmaterial was determined to 250 mg/kg bw/day, resulting in a NOAEL for the substance of 92.5 mg/kg bw/day. This result is read-across to the registered substance, member of the same chemical category.
Executive summary:

A 28 days repeated dose oral toxicity study was conducted with an aqueous solution of a related member of the chemical category (Amphoacetates C8-C18) similar to OECD 407. The aqueous solution was administered 5 times per week (Monday-Friday) in doses of 0, 250, 500 and 1000 mg/kg bw. In females, at 250, 500 and 1000 mg/kg bw/day, a significant increase in absolute liver weight was noted (110, 121 and 121% of controls, respectively). Relative liver weights were also significant increased in all dose groups (104, 109 and 112% of controls, respectively). Although no histopathological changes were noted in liver, the NOAEL was established to be 250 mg/kg bw/day based on a dose-dependent effect on liver weight, resulting in a NOAEL for the substance of 92.5 mg/kg bw/day. This result is read-across to the registered substance, member of the same chemical category.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
92.5 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
One repeated dose study available (conducted with a substance analogue). The study has a Klimisch score 2.
System:
hepatobiliary
Organ:
liver

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A 28 days repeated dose oral toxicity study was conducted with an aqueous solution of a related member of the chemical category (C8-C18 alkyl derivatives) similar to OECD 407. The aqueous solution was administered 5 times per week (Monday-Friday) in doses of 0, 250, 500 and 1000 mg/kg bw. In females, at 250, 500 and 1000 mg/kg bw/day, a significant increase in absolute liver weight was noted (110, 121 and 121% of controls, respectively). Relative liver weights were also significant increased in all dose groups (104, 109 and 112% of controls, respectively). Although no histopathological changes were noted in liver, the NOAEL was established to be 250 mg/kg bw/day based on a dose-dependent effect on liverweight, resulting in a NOAEL for the substance of 92.5 mg/kg bw/day.

The read-across from this other member of the chemical category alkylamphoacetates to the registered substance for the 28 days repeated dose oral toxicity study is considered scientifically justified based on the overall information available (see report for the category approach in IUCLID chapter 13).

Justification for classification or non-classification

Based on the current data-set, the registered substance is not classified for repeated dose toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures.