Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Name: 7-AMCA
Chemical name: 7-Amino-3-methoxy-cefalosporanic acid
Molecular formula: C9H12N2O4S
CAS No.: 24701-69-7
Supplier: Sponsor
Batch No.: 36423006
Certificate of analysis: Available
Purity: 90.1 % on anhydrous basis (HPLC)
Water content: 0.3 %
Solubility: In water 0.1 g/L at 20 °C
In methanol 0.05 g/L
Appearance: Yellowish powder
Conditions of storage: Refrigerator, in the dark. Protected from moisture
Stability: Stable over ca. 6 months under conditions of storage. Stable over several weeks at room temperature
Date of expiry: October 2000

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institut für Labortierkunde und -genetik. Himberg. Austria..
- Age at study initiation: Ca. 8 w (males), 12 weeks (females).
- Weight at study initiation: mean of 270 g for males; mean of 231 g for females.
- Housing: Single caging
- Diet: Altromin 1324 forte ad libitum
- Water: Tap water ad libitum
- Acclimation period: 6 d.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 23
- Humidity (%): ca. 58
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
Hair of the dorsal trunk was clipped with an electrical hair clipper one day before the application of the test substance. The test site was located on the median dorsal thoracal region. A dermal administration was performed once by spreading the test substance on an area of about 10 % of the estimated body surface. An area of 5 x 6 cm was labelled in a relaxed animal. This area, when slightly stretched for the administration, gives an application site of about 50 cm2.
The individual doses were calculated using the body weights determined at the day of the administration. A cellulose patch with the calculated amount of the test substance, spread over an area of approximately 5 x 6 cm and soaked with deionised water to given optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape. Patch and tape were covered semi-occlusively by a dressing.
The duration of exposure was 24 hours.
At the end of the exposure period the dressing, the tape and the patch were removed. Residual test substance was wiped off using wet cellulose tissue.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw.
No. of animals per sex per dose:
5 males + 5 females.
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: 5 times on the first day, then at least once each day.
- Frequency of weighing: before administration, 7 and 14 d p.a.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
3/5 males and 2/5 females were normal during the whole observation period. All other animals were affected: Chromodacryorrhoea, with an onset earliest 1 h after the administration and ending 6 h p.a., is attributed to the discomfort, caused by the dressing which restricts the freedom of movement.
Body weight:
Males and females: A slight body weight loss or a low body weight gain was noted in 1/5 males and in 4/5 females between 0 and 7 d p.a. This might be due to the discomfort, caused by the dressing. Body weight and body weight gain were inconspicuous in all animals between 7 and 14 d p.a.
Gross pathology:
Effects on organs: No relevant changes.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No toxic effects of the test substance were noted in life at the dose of 2000 mg/kg body weight.
Executive summary:

The standard acute dermal toxicity method according to the EU- and OECD-guidelines was applied. The substance was administered in a limit dose of 2000 mg/kg body weight to 5 male and 5 female rats.

No mortality occurred. No relevant toxic effects of the test substance were noted by signs in life and post mortem. The dermal LD50 was determined to >2000 mg/kg body weight.