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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Cross-reference
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
Please see Analogue Approach
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
GLP compliance:
yes
Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
no mortality observed
Description (incidence):
No death ocurred during the study in any of the 3 groups.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Body weight gain was similar in all 3 groups in the 28 days of treatment.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
The food consumption was similar in all 3 groups.
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
There was a significant difference in the sodium and total protein in the satellite group and of calcium in the males. The effects are not considered as caused by the treatment.
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The weight of organs did not show any significant variations in relation to the treatment.
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
No deaths occurred during the study in any of the 3 groups (treated - satellite - control).
No clinical signs were observed during the experimental observation period in all 3 groups. In particular no erythema and/or oedema was observed in the test group.

BODY WEIGHT AND WEIGHT GAIN
Body weight gain was similar in all 3 groups.

FOOD CONSUMPTION
Food consumption was similar in all 3 groups.

HAEMATOLOGY
No significant differences in all 3 groups.

CLINICAL CHEMISTRY
Significant differences were measured in the sodium and total protein of the satellite group. These effects are not considered as caused as relevant.

ORGAN WEIGHTS
The weight of organs did no show any significant variations in relation to the treatment.

GROSS PATHOLOGY
At the ante-mortem examination in all animals no pathological symptoms were observed.
No macroscopic abnormalities related to the treatment were seen at necropsy.
Minor anomalies were observed in 1/5 males and 2/5 females of the test group, 2/5 male and 2/5 females in the control group and 2/5 males and 2/5 females in the satellite group. These minor findings were gastric meteorism, presence of granular tissue on stomach wall, liverworth steatosis, kidney cyst, ovary cyst and spleen iperplasy of white pulp. These changes don't have any toxicological relevance.

Dose descriptor:
NOAEL
Effect level:
10 other: mL/kg bw/day (nominal)
Based on:
test mat.
Remarks:
no remarks
Sex:
male/female
Basis for effect level:
other: no effects
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
NOEL
Effect level:
10 other: mL/kg bw/day (nominal)
Based on:
test mat.
Remarks:
no remarks
Sex:
male/female
Basis for effect level:
other: no effects
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
no remarks
Sex:
male/female
Basis for effect level:
other: no effects
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Critical effects observed:
no
Conclusions:
In experimental conditions, on the basis of a total evaluation of the results obtained, the test material Butanedioic acid, 2,3-dihydroxy-di-C14-C15 alkyl esters did not cause any local or systemic toxicity. The NOAEL was determined to be 10 mL/kg bw/day (1000 mg/kg bw/d).
Executive summary:

The study of subacute dermal toxicity (28 days) was performed on a group of 30 rabbits (20 treated and 10 controls).

The test material, Butanedioic acid, 2,3-dihydroxy-di-C14-C15 alkyl esters, was administered for 4 weeks (5 days out of 7) at daily dose of 10 mL/kg bw (1000 mg/kg bw/d) by dermal application. The test material was administered in sesam oil to 20 animals, while the control group (10 animals) were treated with sesame seed oil.

The animals were sacrificed at the end of treatment, on the 28th days (treated and control groups) with the exception of 10 rabbits which had been treated with the test material, they were kept under observation for another 2 weeks after the end of treatment (satellite group).

During the study animals were observed daily for possible toxicity symptoms. These observations included: evaluation of local reaction in the application aria, evaluation of organ functions, evaluation of the tegumentary apparatus conditions, evaluation of possible variations in somatomotor activity and sensorium conditions, evaluation of mucosae conditions. Animals body weight and food consumed were recorded weekly. At the end of the study a blood taking from heart in all animals was executed in order to evaluate the hematological and hematochemical parameters in the three groups (treated and controls), then an autopsy was performed.

The results obtained from the study can be summarized as follows: No case of mortality and no pathological symptoms were observed in the animals treated and in the control animals, in particular no phenomena of erythema or oedema was observed in the area where the test material was applied.

At the autopsy no pathological anomalie were observed. The weight of the organs showed no significant differences between the 3 groups. The hematological and hematochemical examinations, conducted at the end of the study did not show any significant differences between the groups.

In experimental conditions, on the basis of a total evaluation of the results obtained, the test material Butanedioic acid, 2,3-dihydroxy-di-C14-C15 alkyl esters did not cause any local or general toxicity.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

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