1,6-bis((dibenzylthiocarbamoyl)disulfanyl)hexane

Acute Toxicity: dermal

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

Guideline:

other: OECD 402

GLP compliance:

yes

Test type:

other: acute dermale toxicity

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-280-6

EC Name:

-

Cas Number:

151900-44-6

Molecular formula:

Hill formula: C36H40N2S6 CAS formula: C36H40N2S6

IUPAC Name:

N,N-dibenzyl({6-[(dibenzylcarbamothioyl)disulfanyl]hexyl}disulfanyl)carbothioamide

Details on test material:

purity: 86.3%

Test animals

Species:

rat

Strain:

other: Bor: WISW (SPF Cpb)

Sex:

male/female

Details on test animals or test system 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

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:

other: 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 toxicit

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

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.