Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-Mar-09 to 2011-Mar-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Ministerium für Arbeit, Gesundheit und Soziales Des Landes Nordrhein-Westfalen
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N,N-Caprolactam-disulfide (chemical name: (1,1 '-Dithiobis[hexahydro-2H-azepin-2-one])
- Substance type: organic
- Physical state: solid
- Analytical purity: 99.32 % (not used for calculations)
- Isomers composition:
- Lot/batch No.: Lot 19779/19777
- Expiration date of the lot/batch: 14 DEC 2011
- Storage condition of test material: refrigerator
- Other: Confirmation of the identity of the test item was performed.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: 9 - 13 weeks approximately
- Weight at study initiation: male 287 g - 297 g , female 222g-238 g
- Housing: caged individually in polycarbonate cages on low dust wood granulate bedding (Lignocel BK 8-15, Firma Rettenmaier, Germany). The cages of the animals were placed on racks.
- Diet (e.g. ad libitum): standard diet "Provimi Kliba 3883 PM SI5 Maus/Ratte Haltung, Kaiseraugst Switzerland" ad libitum
- Water (e.g. ad libitum): tap water ad libitum from poly-carbonate bottles
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2°C
- Humidity (%): 55 ±5%
- Air changes (per hr): approx. 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours rhythm

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Groups of 5 male and 5 female Wistar rats received a single dermal dose of 2000 mg/kg body weight of the test item applied semiocclusively for 24 hours.

TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn.
- Area of exposure: approximately 10% of the body surface area (ca. 30 cm²
- % coverage:
- Type of wrap if used: a wet gauze-layer (6.0 cm x 5.0 cm = 30.0 cm2) of a „Cutiplast® steril" coated with air-tight „Leukoflex®". The gauze strip was placed on the rat's back and secured in place using „Peha®-Haft" cohesive stretch tape and additionally covered with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): area was rinsed with tepid water using soap and gently patting the area dry.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): For each dose and animal the required amount of pure solid test substance was calculated on the base of the body weight at time of dosing. Females 14.8 - 15.9 mg/m³, Males 19.1 - 19.8 mg/m³

Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days, clinical signs and mortality rates were determined several times on the day of application and subsequently at least once daily for an observation period of at least 14 days. Mortality and in the event of symptoms occurring, nature, duration and intensity (possible grading: no intensity specified /1 = slight 12 = distinct) were recorded individually.
- Frequency of observations and weighing: weight gain of the animals was checked weekly until the end of the study
- Necropsy of survivors performed: yes, the surviving animals were sacrificed by carbon dioxide at the end of the study, dissected and examined macroscopically.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed. A dose of 2000 mg/kg body weight was tolerated by male and female rats without mortalities, clinical signs, effects on weight development and gross pathological findings.
Clinical signs:
No clinical signs were observed. A dose of 2000 mg/kg body weight was tolerated by male and female rats without mortalities, clinical signs, effects on weight development and gross pathological findings.
Body weight:
There were no toxicologically significant effects on body weight or body weight development in males and females. A dose of 2000 mg/kg body weight was tolerated by male and female rats without mortalities, clinical signs, effects on weight development and gross pathological findings.
Gross pathology:
The necropsies performed at the end of the study revealed no particular findings. A dose of 2000 mg/kg body weight was tolerated by male and female rats without mortalities, clinical signs, effects on weight development and gross pathological findings.
Other findings:
No other findings were observed.

Any other information on results incl. tables

Table1 -Dose-Response
dose mg/kg bw toxicological result* occurrence of signs time of death mortality(%)
male        
2000 0/0/5 - - 0
female        
2000 0/0/5 ~ - 0
*  number of animals which died spontaneously and/or were sacrificed in moribund state / number of animals with signs of toxicity / total number of animals used per group

Table 2 - Animal weights

T9082432 Tiergewichte /body weights(G) Akut/acute 4635/11
Tiernr./animal no. Tag /day nach Tod / Todeszeit /after death / time of d.
1 8 15
2000 mg/kg männlich /male CT
1 287 308 331
2 296 324 357
3 288 307 333
4 297 323 346
5 291 313 343  
m 292 315 342  
s 4.4 8.3 10.5  
2000 mg/kg weiblich /female CT
6 222 232 238
7 230 233 243
8 230 230 231
9 238 243 260
10 234 245 249  
m 231 237 244  
s 6.0 6.7 11.1  

Table 3 - Body weight gain

T9082432 Gewichtsentwicklung /weight gain (G) Akut/acute 4595/11
Tiernr./ animal no. Tag/day Gesamtgew.-Entw./ total weight gain
1 8 15
2000 mg/kg männlich /male CT
1 287 +20 +24 +44
2 296 +28 +33 +61
3 288 + 19 +26 +45
4 297 +27 +22 +49
5 291 +21 +30 +51
m 292 23 27 50
s 4.4 4.0 4.5 6.8
2000 mg/kg weiblich /female CT
6 222 + 10 +6 + 16
7 230 +3 + 10 + 13
8 230 +0 + 1 + 1
9 238 +4 + 17 +22
10 234 + 12 +4 + 16
m 231 6 8 13
s 6.0 4.8 6.4 7.6

Table 4: individual macroscopic findings

Individual    macroscopic findings
All findings
animal no. time / type of death finding
group 01 2000 MG/KG male CT
1 15d / E General observations no pathological finding
2 15d / E General observations no pathological finding
3 15d / E General observations no pathological finding
4 15d / E General observations no pathological finding
5 15d / E General observations no pathological finding
group 02 2000 MG/KG female CT
6 15d / E General observations no pathological finding
7 15d / E General observations no pathological finding
8 15d / E General observations no pathological finding
9 15d / E General observations no pathological finding
10 15d / E General observations no pathological finding

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category V
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD Guideline 402 without deviations and considered to be of the highest quality (reliability Klimisch 1). Caprolactam disulphide was shown not to produce any significant clinical signs or toxicological effects after dermal application in rats. Based on the present investigations, the test item is regarded to have the following LD50 values: LD50 rat, male > 2000 mg/kg body weight and LD50 rat, female > 2000 mg/kg body weight. So it is regarded as non-toxic after dermal application (GHS Category 5/unclassified analogous OECD draft guideline 434).
Executive summary:

A study on the acute dermal toxicity of N,N'-Caprolactam disulfide was conducted in male and female Wistar rats according to the OECD Guideline 402 - Acute Dermal Toxicity and according to EU-Method B.3 without deviations (Gillissen, 2011). The study was conducted according to the principles of good laboratory practice and considered to be of highest reliability (Klimisch 1). Groups of 5 male and 5 female Wistar rats received a single dermal dose of 2000 mg/kg body weight of the test item applied semiocclusively for 24 hours.. No mortality, clinical signs or toxicologically significant effects on body weight/body weight gain were observed. Therefore the test substance has an LD50 more than 2000 mg/kg bw and the test item is considered to be not toxic after dermal application to rats.