Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was done with a formulation having a different composition (70% Chloroacetamide; 30% sodium benzoate), however it was considered reliable, adequate and relevant for classification and local DNEL calculation. As there is no clinical biochemistry and only limited histopathology, the study cannot be used for systemic DNELs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report Date:
1971

Materials and methods

Principles of method if other than guideline:
IBR guideline
GLP compliance:
no
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Konservierungsmittel CA 24; CA 24
- Physical state: White, fine crystalline powder
- Composition of test material, percentage of components: Technical mixture: 70% chloroacetamide, 30% sodium benzoate DAB 7
- Other: Firma Biochema Schaben, Memmingen

Test animals

Species:
rat
Strain:
other: Wistar SPF
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Paderborn
- Age at study initiation: Adult
- Weight at study initiation: Average ca. 210 g
- Housing: Individual cages
- Diet: Rattenstandardiät (ssniff/Intermast), ad libitum
- Water: Ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%):45-55%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
open
Vehicle:
water
Details on exposure:
The test substance was dissolved in water, pure or supplied with 1-2 % Lanette R.
Back of animals had been partly shorn.
Using a glass rod, the test solution was applied daily onto the shorn areas.
Duration of treatment / exposure:
3 months / 13 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 12.5, 50.0 mg/kg
Basis:
nominal per unit body weight
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Details on study design:
Control: Lanette; Group I, 12.5 mg/kg in Lanette 1 %; Group II, 50.0 mg/kg in Lanette 2 %; Group III, 50.0 mg/kg in aqua dest 2 %;

Examinations

Observations and examinations performed and frequency:
clinical symptoms : daily
body weight, weight gains, feed use, feed efficiency, water used : weekly
Sacrifice and pathology:
section: weights of heart, liver, kidneys, adrenal glands, testicles
histology: testicles

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: clinical signs; mortality; body weight; food consumption; gross pathology; organ weights; histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The dermal “no-effect” level of CA 24 in male adult rats is 50 mg/kg bw.
Executive summary:

In a 13 weeks dermal toxicity repeated dose study, Konservierungsmittel CA 24 was applied to the shaved backs of male adult Wistar-rats, at doses of 12.5 and 50.0 mg/kg in Lanette or Aqua dest. Neither test dependent or substance specific changes were observed in the growth parameters and histomorphological examinations. The dermal “no-effect” level of CA 24 in male adult rats is 50 mg/kg bw.