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Description of key information

Oral, rat: The key study is a study with the structural analogue branched AKD (P-2290, CAS 849705-80-2, Huntingdon 1999) performed according to current guidelines and under GLP. The LD50 from this study is > 2000 mg/kg bw.
Dermal, rat: The acute LD50 for rats of the structural analogue branched AKD (P-2290; Huntingdon 1999) was demonstrated to be > 2000 mg/kg bodyweight per formed according OECD TG 402 and GLP.
For acute inhalation toxicity a valid study is not available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
weight of evidence, see attached document
Adequacy of study:
weight of evidence
Justification for type of information:
see attachment
Reason / purpose for cross-reference:
reference to other study
Reason / purpose for cross-reference:
reference to other study
Reason / purpose for cross-reference:
reference to other study
Reason / purpose for cross-reference:
read-across: supporting information
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Remarks on result:
not measured/tested
Remarks:
Based on read-across and weight of evidence approach, see attached document
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the substance is >2000 mg/kg bw
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Remarks:
based on surrogate substance
Adequacy of study:
key study
Study period:
10 August 1998 - 1 September 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to international guidelines and under GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 88-101g
- Fasting period before study: Access to food only was prevented overnight prior to and for approximately 4 hours after dosing.
- Housing: Rats were allocated without conscious bias to cages within the treatment group and housed in groups of five rats of the same sex in metal cages with grid floors in Building R14 Room 6.
- Diet (e.g. ad libitum): ad libitum, standard laboratory rodent diet. The batch of diet used for the study was analysed for certain nutrients, possible contaminants and microorganisms.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-26
- Humidity (%): 39-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 10 August 1998 - 1 September 1998
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.27 ml/kg bodyweight (specific gravity 0.8813).

DOSAGE PREPARATION (if unusual): Due to the physical characteristics of the test material at room temperature, P-2290 was warmed in a water bath (44°C) until melted, prior to dosing.
Doses:
Sighting study
500 mg/kg bw or 2000 mg/kg bw.

Main study
2000 mg/kg bodyweight. .
No. of animals per sex per dose:
Sighting study
Two female rats.

Main study
A group of ten rats (five males and five females).
Control animals:
no
Details on study design:
- Duration of observation period following administration: Animals in the sighting study were observed for seven days afier dosing. Animals in the main study were observed for 14 days after dosing.
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities. Animals were observed soon afier dosing and at frequent intervals for the remainder of Day 1. On subsequent days, surviving animals were observed once in the morning and again at the end of the experimental day (with the exception of the last day of observation - morning only). The nature and severity of the clinical signs and time were recorded at each observation. The bodyweight of each rat in the main study was recorded on Days 1, (prior to dosing), 2, 3, 4, 8, and 15, or at death. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: All animals were subjected to a macroscopic examination which consisted of opening the cranial, abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.
Statistics:
Not applicable
Preliminary study:
Initially, one female rat was dosed at 500 mg/kg bodyweight. Clinical signs in this animal were confined to piloerection and hunched posture. Recovery was complete by Day 4. Bodyweight gain was considered satisfactory for studies of this nature and duration and no macroscopic abnormalities were noted at the terminal necropsy on Day 8.
Subsequently, in accordance with the study guideline, a further female was treated at 2000 mg/kg bodyweight. Clinical signs in this animal comprised piloerection, hunched posture and increased salivation. Recovery was complete by Day 2. Bodyweight gain was considered satisfactory for studies of this nature and duration and no macroscopic abnormalities were noted at the terminal necropsy on Day 8.
Since the sighting study indicated that the discriminating dose was expected to be 2000 mg/kg bodyweight, this dose level was selected in compliance with the study guideline, as a suitable dosage for the main study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: No mortalities were observed.
Mortality:
None
Clinical signs:
Piloerection was observed in all rats immediately following dosing. This sign persisted and was accompanied in all rats later in the study by hunched posture and waddling/unsteady gait. In addition, abnormal faeces (seen in two males and two females) and ungroomed appearance (seen in one male and all females) were also observed. Recovery of rats was complete in all animals by Day 2.
Body weight:
All rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination of animals killed at study termination on Day 15 revealed no abnormalities.
Other findings:
None
Interpretation of results:
study cannot be used for classification
Conclusions:
A limit study showed that the LD50 is > 2000 mg/kg bw. Other supporting information shows that the LD50 is > 5000 mg/kg bw. Thereforre the test substance is not classified under GHS although in this study the dose was not higher than 2000 mg/kg bw.
Executive summary:

This study was performed to assess the acute oral toxicity of P-2290 to the rat. The method followed was that described in: EEC Methods for the determination of toxicity, Annex to Directive 92/69EEC (OJ No. L383A, 29.12.92), Part B, Method B. 1 bis. Acute toxicity (oral) - fixed dose method. OECD Guideline for Testing of Chemicals No.420 'Acute Oral Toxicity - Fixed Dose Method' Adopted 17 July 1992. A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied by the Sponsor, at a dose level of 2000 mg/kg bodyweight. This dose level was chosen after review of results from a sighting study. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There were no deaths. Clinical signs of reaction to treatment were confined to piloerection, hunched posture and waddlingiunsteady gait, seen in all rat. In addition, abnormal faeces and ungroomed appearance were less commonly observed. Recovery of rats was complete in all instances by Day 2. All rats were considered to have achieved satisfactory bodyweight gains throughout the study. Macroscopic examination of animals killed at study termination on Day 15 revealed no abnormalities. The LD50 is > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
In a weight of evidence approach based on data on the substance and a close analogue, it was concluded that the LD50 of the substance is > 2000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study waived based on low acute oral toxicity and a study on a structural analogue.

Additional information

Oral


The key study is a study with the structural analogue P-2290 (Huntingdon 1999) performed according to current guidelines and under GLP. The LD50 from this study is > 2000 mg/kg bw. No mortalities occurred in this study.


 


There are three oral tests available with linear AKD to support the key study (with Stearyldiketen TV 194/37 (BASF 1976), Alkyl Ketene Dimers batch 339 (Eka 1988), and Aquapel 380 (ITL 1954)). The first study was performed before OECD test guidelines and GLP were established. The documentation is according to the best practice at the time the study was performed. However, some critical details of the test protocol and the results are not available. This study gave an LD50 of >10,000 mg/kg b.w. in Wistar rats.


 


The second available study, a limit test with Alkyl Ketene Dimers batch 339, performed according to OECD TG 401, resulted in an oral LD50 >2000 mg/kg bw . Unfortunately, the report could not be found so the validity of this study could not be verified.


 


The third study gave an oral LD50 of >10 000 mg/kg bw, but unfortunately there was insufficient detail available to judge the validity of this study.


 


Dermal


The acute dermal LD50 for rats of branched AKD (P-2290) was demonstrated to be > 2000 mg/kg bodyweight per formed according OECD TG 402 and GLP. There was no systemic response in any animal throughout the study. Slight to well-defined dermal irritation was noted in three animals, resolving in all instances by Day 7. No dermal response to treatment was recorded for any other animal throughout the study.


 


An LD50 of 6730 mg/kg bw in rabbits with linear AKD was given in the ECB-published IUCLID (February 19, 2000). The study report is, however, no longer available. The reliability of this data cannot be confirmed.


 


The key study performed with branched AKD in rats reports a LD50> 2000 mg/kg bw. No mortalities occurred in this limit study.


 


Inhalation


For acute inhalation toxicity a valid study is not available. Information on acute toxicity is available for the oral route and for the dermal route. Since the substance is a wax, exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.

Justification for classification or non-classification

Data is available for acute oral and acute dermal toxicity based on studies on a structural analogue and a weight of evidence aproach based on the substance itself. These data do not justify classification for these endpoints.