Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral:
Data from direct determination of toxicity of sodium caprolactamate as defined in section 1. Sodium caprolactamate is harmful if swallowed. LD50 oral (rat) = 300-2,000 mg/kg bw (female). For calculation the LD50 value 1450 mg/kg derived from epsilon-Caprolactam will be used.
Acute toxicity, inhalative:
Data from epsilon-Caprolactam will be used (a safety factor of 2 is applied): LC50 inhalative = 3.5 mg/L.
Acute toxicity, dermal:
The substance is corrosive to skin; therefore no toxicity data can be transferred from epsilon-Caprolactam. The substance has to be classified accordingly.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2,000 mg/kg
300 mg/kg
No. of animals per sex per dose:
Treated group (2000 mg/kg): 6 female rats
Treated group (300 mg/kg): 6 female rats
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test item. The animals were weighed on day D0 (just before administering the test item) then on D2, D7, and D14.
Weight changes were calculated and recorded.
- Necropsy of survivors performed: On D14, the animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels.
- Other examinations performed: Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view to microscopic exanimations.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
It was noted the death of 4 treated rats treated at 2000 mg/kg b.w., 7, 8 and 24 hours after the test item administration.
No mortality occurred in the animals treated at 300 mg/kg b.w..
Clinical signs:
It was registered in the animals treated at 2000 mg/kg, 30 minutes after the test item administration, a decrease of the spontaneous activity (6/6) associated with a piloerection (4/6) and a decrease of the righting reflex (1/6) at the reading time 4 hours. The surviving animals recovered a normal activity the 2nd day of the test.
No clinical signs related to the administration of the test item at 300 mg/kg were observed.
Body weight:
It was noted a body weight decrease (-4%) on the surviving animals treated at 2000 mg/kg b.w., 48 hours after the test item administration. Then the body weight evolution of the animals remained normal throughout the study.
The body weight evolution of the animals treated at 300 mg/kg remained normal throughout the study.
Gross pathology:
The macroscopical examination of the animals treated at 2000 mg/kg which died during the test revealed the presence of black foci on the corpus and a decrease of vascularisation on the forestomach (4/4).
The macroscopical examination of the animals treated at 2000 mg/kg at the end of the study revealed a
white thickening layer at the level of the forestomach (2/2).
The macroscopical examination of the animals treated at 300 mg/kg at the end of the study did not reveal treatment-related changes.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50>300 mg/kg bw
LD50<2,000 mg/kg bw
Executive summary:

In conclusion, the LD50 cut-off of the test item Sodium caprolactamate in caprolactam is 2000 mg/kg

body weight by oral route in the rat.

In accordance with the Globally Harmonized System (COM(2007)355 final), the test item needs to be

classified in category 4. The signal work “warning” and hazard statement H302 “Harmful if

swallowed” are required.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
300 mg/kg bw
Quality of whole database:
Good, several GLP guideline studies available

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to the Read-across Statement attached in Section 13.2.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The underlying hypothesis for the read-across is that the target substance is very prone to hydrolysis resulting in the formation of epsilon-caprolactam and sodium hydroxide. As hydrolysis of the target substance will inevitably occur both under physiological and under environmental conditions, the evaluation of the data of epsilon-caprolactam and sodium hydroxide is considered to be sufficient for hazard assessment. Thus, the toxicological behavior of BRUGGOLEN® C10 can be considered to be determined by the hydrolysis products caprolactam and caustic soda.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Target substance: sodium caprolactamate, CAS-No. 2123-24-2 (for detailed composition please refer to the Read-across Statement attached in Section 13.2)
Source substances: epsilon-caprolactam, CAS-No. 105-60-2 and sodium hydroxide, CAS-No. 1310-73-2

3. ANALOGUE APPROACH JUSTIFICATION
The justification of the read-across hypothesis is mainly based on the hydrolysis of the target substance into the source substances.
BRUGGOLEN® C10 is a combination of sodium caprolactamate (17 – 20 %) and epsilon-caprolactam (80 – 83 %). If diluted in water, sodium caprolactamate easily degrades to caprolactam and sodium hydroxide (caustic soda). Reason is the instability of the ionic N-Na-bond of the sodium caprolactamate.
Thus, the toxicological behavior of BRUGGOLEN® C10 can be considered to be determined by the hydrolysis products caprolactam and caustic soda.

4. DATA MATRIX
Please refer to the Read-across Statement attached in Section 13.2.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
8.16 mg/L air
95% CL:
7.2 - <= 9.23
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
9.6 mg/L air (analytical)
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
7.08 mg/L air (analytical)
95% CL:
5.87 - <= 8.1
Exp. duration:
4 h
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
3 500 mg/m³
Quality of whole database:
Acceptable.
The LC50 is estimated from the lowest LC50 of epsilon-Caprolactam resulting in an ATE =3.5.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
GLP study with substance itself

Justification for selection of acute toxicity – inhalation endpoint
Sodium caprolactamate hydrolyses under physiological conditions with the formation of epsilon-Caprolactam and sodium hydroxide, cross-reading from toxicological studies of epsilon-Caprolactam is justified. Therefore in spite of the corrosivness of sodium caprolactamate, also the effects of epsilon-caprolactame have to be taken into consideration. The study allows to estimate the acute toxicity via inhalation route.

Justification for classification or non-classification

Classification of the toxicity of the substance (including read-across from epsilon-Caprolactam) based on section 3.1.3.6.2.3 of CLP Regulation:

Oral:            ATE = 500: acute oral category 4, H 302

Dermal:       Corrosive, no acute dermal classification

Inhalative:   ATE = 3.5: acute inhalative category 4, H 332