Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (e.g. rel. low purity of test substance 86.3%)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 402
GLP compliance:
yes
Test type:
other: acute dermale toxicity
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: 86.3%

Test animals

Species:
rat
Strain:
other: Bor: WISW (SPF Cpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: Winkelmann Co, 4799 Borchen
- Weight at study initiation: 200-300 g
- Fasting period before study:
- Housing:separated by sex, max. 5 animals per Makrolon type III cage
- Diet:ad libitum
- Water: ad libitum
- Acclimation period: at least 5 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30-70%
- Photoperiod (12hrs dark / 12hrs light)


Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: intact dorsal skin, 6.67 cm3/kg bw
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with corn oil MEH 56


Duration of exposure:
4 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 1/2, 1, 2, 3, 4, 5, and 6 h post application as well as once daily during the following 14 days
- Frequency of observations and weighing: day 0, day 7, day 14
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
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:
Signs of toxicity related to dose levels:
Substanzbedingte Vergiftungssymptome traten nicht auf. Alle
Tiere zeigten während der 14tägigen Beobachtungsperiode eine
normale Körpergewichtsentwicklung.
"ENGLISH"
No substance related symptoms of toxicity occured. All
animals showed a normal body weight development during the
observation period.
Gross pathology:
Effects on organs:
Keine Hinweise auf substanzbedingte Organveränderungen bei
den Sektionen und makroskopischen Untersuchungen.
"ENGLISH"
No indications of substance related changes of the organs
occured during the sections and macroscopic investigations.
Other findings:
Signs of toxicity (local):
Es traten weder bei den männlichen noch bei den weiblichen
Tieren substanzbedingte Vergiftungserscheinungen auf. Im
Applikationsbereich wurde 72 h nach Substanzverabreichung
bei drei weiblichen Tieren Schuppenbildung auf der Haut
beobachtet; zwei Tiere zeigten zusätzlich eine Hautrötung.
Nach Ablösung der Schuppen am 7. Tag post applicationem (2
Tiere), am 9. Tag post applicationem (1 Tier) stellte sich
die Applikationsfläche ohne Befund dar. Fünf männliche und
zwei weibliche Tiere zeigten zu keinem Beobachtungszeitpunkt
eine Hautveränderung.

"ENGLISH"
Neither the male nor the female animals showed substance
related symptoms of toxicity.
72 hours after the application of the substance three female
test animals showed scale formation of the skin in the
application range; two animals showed as well redness of the
skin. After the scales came off after the application
(7. day 2 animals, 9. day 1 animal the treated area was
without any findings. Five male and two female animals never
showed changes of the skin during the observation period.

Any other information on results incl. tables

Mortality:

Male: 2000 mg/kg bw; 0/5; females 0/5

Clinical Signs:

No substance related symptoms of toxicity occured. All animals showed a normal body weight development during the observation period.

Gross pathology:

No indications of substance related changes of the organs occured during the sections and macroscopic investigations.There were no changes of the skin or in the subcutaneous tissue in the region of application.

Other findings:

72 hours after the application of the substance three female test animals showed scale formation of the skin in the application range; two animals showed as well redness of the skin. After the scales came off after the application (7. day 2 animals, 9. day 1 animal the treated area was without any findings. Five male and two female animals never showed changes of the skin during the observation period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
LD50 after dermal exposure was >2000 mg/kg bw.
Executive summary:

In rats the LD50 after dermal exposure was >2000 mg/kg bw. This dermal acute toxicity study was done under GLP according to OECD guideline 402 (Hüls AG 1992b). No effects were observed with regard to mortality, clinical signs, body weight and gross examinations. However, scale formation in the region of application was observed in three of five animals 72 hours post application. This effect was reversible within 9 days. In addition, two of these animals showed skin redness 72 hours after the application. Although,

no changes of the skin or in the subcutaneous tissue in the application area were found in any of the animals.