Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11-03-09 - 11-03-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented GLP guideline 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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Ministerium für Arbeit, Gesundheit und Soziales Des Landes Nordrhein-Westfalen
Test type:
acute toxic class method
Limit test:
no

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.

The analytical data verify that the test item formulations are stable at room temperature for at least 2 hours and that the test item is homogeneously distributed in the 5 and 200 mg/mL formulations. Suspensions had to be stirred for homogenization.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: 8 - 12 weeks approximately
- Weight at study initiation: 169 g-181 g
- Fasting period before study: 16 - 24 hours
- Housing: caged conventionally 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

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
The test item was formulated in tap water with the aid of 2% Cremophor EL.
- Amount of vehicle (if gavage): 10 mL/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

OTHER
The applied formulations were well mixed before administration. The formulations for administration were prepared at room temperature. The individual administration volumes were calculated on the base of the body weight at time of administration and were administered in a single oral administration by gavage.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females
Control animals:
no
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 administration and subsequently at least once daily for an observation period of at least 14 days.
- Frequency of observations and weighing: the weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes, animals which died or were killed in moribund state were weighed (except on day of administration) and dissected as soon as possible, and examined macroscopically. 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 levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
A dose of 2000 mg/kg body weight was tolerated by female rats without clinical signs, effects on weight gain and gross pathological findings. One animal died during the observation period without clinical signs and any treatment-related findings.
Clinical signs:
No clinical signs were observed. A dose of 2000 mg/kg body weight was tolerated by female rats without clinical signs, effects on weight gain and gross pathological findings. One animal died during the observation period without clinical signs and any treatment-related findings.
Body weight:
There were no toxicologically significant effects on body weight or body weight gain in the surviving animals. A dose of 2000 mg/kg body weight was tolerated by female rats without clinical signs, effects on weight gain and gross pathological findings. One animal died during the observation period without clinical signs and any treatment-related findings.
Gross pathology:
The necropsies performed in the animal that died during the observation period and at the end of the study revealed no particular findings A dose of 2000 mg/kg body weight was tolerated by female rats without clinical signs, effects on weight gain and gross pathological findings. One animal died during the observation period without clinical signs and any treatment-related findings.
Other findings:
No other findings were observed.

Any other information on results incl. tables

Table 1 - Dose-Response
dose mg/kg bw toxicological result* occurrence of signs time of death mortality (%)
female
(1st)2000 1/0/3 - 3d 33
(2nd)2000 0/0/3 -- - 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 LD50 oral: >2000 mg/kg bw- equivalent to Category 5 of the GHS and LD 50 cut off 2500 mg/kg bw according to OECD Test Guideline 423

Table 2 - Animal weights

T8082431 Tiergewichte / body weights (G) Akut/acute 4615/11
Tiernr./ Tag / day nach Tod / Todeszeit / after death / time of death
animal no. 1 8 15
2000    MG/KG  weiblich / female PO    
1 169 163 3d
2 173 198 215
3 176 197 214
4 181 195 209
5 179 190 191
6 179 198 199    
m 176 196 205    
s 4.6 3.3 10.3    

Table 3 - Animal weight gain

T8082431 Gewichtsentwicklung / weight gain (G) Akut/acute 4625/11
Tiernr./animal no. Tag / day Gesamtgew.-Entw./ total weight gain
1 8 15
2000    MG/KG  weiblich / female PO  
1 169 - - -
2 173 +26 + 16 +42
3 176 +21 + 17 +38
4 181 + 14 + 14 +29
5 179 + 11 + 1 + 12
6 179 + 18 + 1 +20
m 176 18 10 28
s 4.6 5.6 8.2 12.5

Table 4 - Individual findings

Individual    macroscopic findings
All findings
animal no. time / type of death finding
     
group 01 2000 MG/K 3  female PO
1 3d / T General observations no pathological finding
2 15d / E General observations no pathological finding
3 15d / E General observations no pathological finding
group 02 2000 MG/K 3  female PO
4 15d / E General observations no pathological finding
5 15d / E General observations no pathological finding
6 15d / E General observations no pathological finding

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
The study was performed according to the OECD Guideline 423 without deviations and considered to be of the highest quality (reliability Klimisch 1). Caprolactam disulphide was shown not to produce any significant clinical signs of toxicological effects in rats. According to OECD guideline 423 the LD50 cut-off of the test item is 2500 mg/kg bw. According to EU Directive 67/548/EEC and EC Regulation 1272/2008 the test item is unclassified. So it is regarded as non-toxic after oral application.
Executive summary:

A study on the acute oral toxicity of N,N'-Caprolactam disulfide was conducted in female Wistar rats according to the OECD Guideline 423 - Acute Oral Toxicity - Acute Toxic Class Method and EU-Method B.1 without deviations (Gillissen, 2011) and according to the principles of good laboratory practice. Therefore the study was considered to be of the highest reliability (Klimisch 1). As dose 2000 mg/kg bw of the test substance was administered via gavage to the rats. Observations were made for a period of 14 days. No clinical signs or toxicologically significant effects on body weight or body weight gain were observed. One female rat died during the observation period, without clinical signs and any treatment-related findings. The acute oral median lethal dose (LD50) of the test material in rats observed over a period of 14 days was estimated to be greater than 2000 mg/kg bw.