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Administrative data

Description of key information

The acute oral LD50 was 2,330 mg/kg bw (rat) with central nervous system stimulation (trembling, convulsive twitches, ataxia) as the main clinical sign appearing at about 1,580 mg/kg bw. The dermal LD50 was greater than 2,000 mg/kg bw (rat). Decreased food consumption and stagnation of body weight development were noted. Valid acute inhalation studies in rats are not avail

Among the existing valid studies following three studies were found to show the highest toxicity after oral, dermal and inhalativ application of isophorone: The acute toxicity in laboratory animals is low to moderate with an oral LD50 (rat) of 1500 mg/kg bw (Günzel and Richter, Schering AG, 1968), a dermal LD50 (rabbit) of 1200 mg/kg bw (Dutertre-Catella, 1976) and an inhalative LC50 (rat, aerosol) of 7000 mg/m3 air (Esso Research, 1965).

Among the existing valid studies following three studies were found to show the highest toxicity after oral, dermal and inhalativ application of isophorone: The acute toxicity in laboratory animals is low to moderate with an oral LD50 (rat) of 1500 mg/kg bw (Günzel and Richter, Schering AG, 1968), a dermal LD50 (rabbit) of 1200 mg/kg bw (Dutertre-Catella, 1976) and an inhalative LC50 (rat, aerosol) of 7000 mg/m3 air (Esso Research, 1965).

Among the existing valid studies following three studies were found to show the highest toxicity after oral, dermal and inhalativ application of isophorone: The acute toxicity in laboratory animals is low to moderate with an oral LD50 (rat) of 1500 mg/kg bw (Günzel and Richter, Schering AG, 1968), a dermal LD50 (rabbit) of 1200 mg/kg bw (Dutertre-Catella, 1976) and an inhalative LC50 (rat, aerosol) of 7000 mg/m3 air (Esso Research, 1965).


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:
1985-01-09 - 1985-01-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Strain: Wistar (Bor: WISW (SPF TNO))
- Source: Winkelmann, Borchen (Germany)
- Weight at study initiation:
females 117 g, males 126 g (mean) environmental conditions: Feed: R 10 complete feed for rats (Ssniff, Soest; Germany); Water: tap water ad libitum; Room temperature: 20°C (+/- 1°C); Humidity: 60% (+/- 5%), Air change: 15 times per hour; illumination: 12 hour light/dark rhythm
Route of administration:
oral: gavage
Vehicle:
other: fatty alcohol ethoxylate (Cremophor EL)
Details on oral exposure:
- Test substance preparation: the test substance was finely ground in a mortar, mixed with cremophor EL, stirred in an Ultra-Turrax and then heated to 40 °C.
- Single dose after 16 h of fasting
- Volume administered or concentration: 20 ml/kg
Doses:
- Doses: 1580 / 1990 / 2510 / 3160 mg/kg bw (gavage),
selected after screening test with small number of animals
No. of animals per sex per dose:
5; highest dose: 10
Control animals:
no
Details on study design:
- Post dose observation period: 14 days
EXAMINATIONS:
- body weight: before and on days 1, 7, 14 after treatment
- clinical signs: up to 6 hours after treatment, then daily
- gross pathology at the end of investigation
Statistics:
Litchfield and Wilcoxon (1949), J. Pharmacol. Exp. Ther. 96, 99
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 330 mg/kg bw
95% CL:
2 044 - 2 656
Mortality:
1580 mg/kg: none
1990 mg/kg: 3 males, 1 female, within 24 hours
2510 mg/kg: 1 male, 5 females, within 24 hours
3160 mg/kg: 8 males, 7 females, within 72 hours
Clinical signs:
Observed in all dosed animals: About 10 to 15 minutes after adminstration, the animals took a prone position and showed convulsive twitches, tremor and Straub's phenomenon. After half an hour, the animals took a lateral position, had a ruffled fur and continued to show convulsive twitches and impairment of breathing. Later on, moderate to severe sedation and ataxia, salivation, hypothermia, staggering, crouched posture, closed or small dark eyes and, in some animals, diarrhea were observed. After 2-3 days, the animals showed a ruffled fur, increase in motility and, in part, vocalisation when being touched. Signs of toxicity had disappeared after 11 days in the animals of the three lower dose groups, while the animals of the highest dose group (3160 mg/kg) showed signs of toxicity during the 14-day observation period.
Body weight:
Increase of body weight was practically unaffected by the treatment.
Gross pathology:
Post-mortem dissection revealed hyperaemia of the gastric and intestinal mucosae, hyperaemia of the lungs, light-coloured spots on the liver and liver congestion. Dissection at the end of the experiment also revealed hyperaemia of the gastric and intestinal mucosae in some animals.
Other findings:
no further information
no further remarks
Conclusions:
In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item Dodecane-12-lactam (lauryl lactame) is 2330 mg/kg of body weight. Under the conditions of this study the acute toxicity of Dodecane-12-lactam (lauryl lactame) afer oral application in rats is very low.
Executive summary:

In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the test item Dodecane-12-lactam (lauryl lactame) is 2330 mg/kg of body weight. In few cases, the treated animals showed signs of toxicity during the 14 day observation period. There was no influence on the increase in body weight. Dissection at the end of the experiment revealed hyperaemia of the gastric and intestinal mucosae in some animals.

Under the conditions of this study the acute toxicity of Dodecane-12-lactam (lauryl lactame) after oral application in rats is very low.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 330 mg/kg bw
Quality of whole database:
Klimisch 1 (reliable without restrictions)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited documentation
Principles of method if other than guideline:
see "Details on dermal exposure" and "Details on study design"
GLP compliance:
no
Test type:
other: single dose was used
Limit test:
yes
Specific details on test material used for the study:
Lauryl lactam supplied by Elf Atochem, purity not stated
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation:
- 5 male and 5 female rats, supplied from IFFA-CREDO
325-374 g, mean 356 g (males)
220-270 g, mean 236 g (females)
- Controls: untreated. No details reported.
Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Details on dermal exposure:
- test substance preparation: the test substance was ground to fine powder and suspended in 1% aqueous carboxy methyl cellulose
- to the shaved back of the animals
- Occlusion: yes, for 24 hours
- Vehicle: 1 % carboxy methylcellulose (CMC) aqueous suspension
- Concentration in vehicle: 40 %
- Total volume applied: 5 ml/kg bw
- Removal of test substance: yes, washed off with lukewarm water 24 hours after administration.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
EXAMINATIONS:
- clinical observations after end of exposure,
repeated during next hours, and
repeated daily for 14 days
- autopsy after 14 days observation period.
Statistics:
no data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortalities
Clinical signs:
Slight decrease in food comsumption (no quantitative data presented)
Body weight:
Stagnation of body weight development (356, 352, 354 g mean body weight for males at d1, d7 and d14, respectively; 237, 236, 240 g mean body weight for females at d1, d7 and d14, respectively).
Gross pathology:
No findings
Other findings:
IRRITATION: no skin effects at all were noted.

no further remarks

Conclusions:
In a determination of the acute dermal toxicity on male and female rats it was found that the LD50 of the test item Dodecane-12-lactam (lauryl lactame) is above 2000 mg/kg of body weight. Under the conditions of this study the acute toxicity of Dodecane-12-lactam (lauryl lactame) afer dermal application in rats is very low.
Executive summary:

The test item Dodecane-12 -lactam (lauryl lactame) was applicated at the skin of the male and female rats in a dose of 2000 mg/kg body weight. No mortalities were observed at this dose. Hence the LD50 of the acute dermal toxicity on male and female rats is above 2000 mg/kg of body weight for the test item Dodecane-12-lactam (lauryl lactame) in rats.

Under the conditions of this study the acute toxicity of Dodecane-12-lactam (lauryl lactame) afer dermal application in rats is very low.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch 2 (reliable with restrictions)

Additional information

Studies in Animals

Dermal

In a limit test with rats, no mortality occurred after dermal treatment with 2000 mg/kg bw for 24 hours under occlusive conditions. The treatment did not produce any adverse skin effects and clinical signs were limited to a slight decrease in food consumption and stagnation of body weight development, which also might have been caused by the constraints of the occlusive treatment. No abnormalities were observed at necropsy (Centre de Recherche et d'Elevage des Oncins, 1975).

Oral

After oral application the LD50 for rats was found to be 2330 mg/kg bw in a test performed according to OECD TG 401 (1981) at dose levels of 1580, 1990, 2510, and 3160 mg/kg bw. Clinical signs observed at doses ≥ 1580 mg/kg bw included prone position, convulsive twitches, tremor and impairment of breathing, followed by sedation and ataxia, salivation, hypothermia, staggering, crouched posture, and closed or small dark eyes. After 2 - 3 days, the animals showed an increase in motility and, in part, vocalization when being touched. Signs of toxicity disappeared after 11 days in the animals dosed with up to 2510 mg/kg bw. Necropsy findings of animals that died during the study revealed hyperaemia of the gastric and intestinal mucosae, hyperaemia of the lungs, light-coloured spots on the liver and liver congestion. Hyperaemia of the gastric and intestinal mucosae were also found in some animals necropsied at the end of the study (Hüls AG, 1985). In a further study the LD50 for rats was determined to be 2600 mg/kg bw ( Centre de Recherche et d'Elevage des Oncins, 1975).

Inhalation

Valid acute inhalation studies are not available.

 

Studies in Humans

No information is available regarding dermal, inhalation and oral acute toxicity.

Justification for classification or non-classification

According to the criteria of EC Directive 67/548/EEC and EC Regulation 1272/2008 and based on the results of the studies Dodecane-12-lactam is not classified.