Registration Dossier

Administrative data

Description of key information

 

The key oral study, conducted in a manner similar to (the now deleted) OECD 401 involved gavage administration of one of five doses of a 60% solution of CHPTAC to male and female rats. An LD50 value of 3.2 mL/kg bw was reported (equivalent to 3688 mg/kg bw, or 2213 mg/kg bw for pure CHPTAC).

 

The key dermal study, conducted according to OECD 402, involved 24-h occluded contact with the test material (65% aqueous CHPTAC). An LD50 value in rats greater than 2348 mg/kg bw was derived for the test material, that has been said to equate to 1526 mg/kg bw for 100% CHPTAC.

 

No suitable data are available for the inhalation route.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific pinciples
Principles of method if other than guideline:
Method: other: LD50 was calculated according to the method of Weil (Biometrics 8 (1952), 249-263)

Method similar to the (now deleted) OECD 401.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: SPF-bred albino rats (Cpb: WU; Wistar random)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the breeding of laboratory animals, TNO, Zeist, NETHERLANDS.
- Weight at study initiation: 84-116 g (males); 76-100 g (females)
- Fasting period before study: not stated
- Housing: stainless steel cage (numer/cage not stated)
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1
- Humidity (%): no data
- Air changes (per hr): 'well ventilated'
- Photoperiod (hrs dark / hrs light): no data

Route of administration:
oral: gavage
Vehicle:
other: undiluted
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:


MAXIMUM DOSE VOLUME APPLIED:
Doses:
1.92, 2.30, 2.76, 3.31, 3.98 mg/kg body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighed on days 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 according to: Weil (1952). Biometrics 8, 249.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3.2 mL/kg bw
95% CL:
2.66 - 3.84
Remarks on result:
other: 60% CHPTAC
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 688 mg/kg bw
Remarks on result:
other: 60% CHPTAC
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 213 mg/kg bw
Remarks on result:
other: 100% CHPTAC
Mortality:
See Table 1 in "Any other information on results incl. tables".
Clinical signs:
No clinical signs amongst survivors.
Body weight:
No treatment-related effect on body weight.
Gross pathology:
No abnormal gross pathology.
Other findings:
None reported.

Table 1: Mortality

 Dose
(ml/kg bw)

Mortality (dead/total)

Male

Female

Combined

1.67

1/5

0/5

1/10

2.00

0/5

1/5

1/10

2.40

2/5

1/5

3/10

2.88

4/5

3/5

7/10

3.46

4/5

2/5

6/10

Death occurred within 1 h of dosing; survivors recovered and there were no overt signs of toxicity. No gross abnormalities were identified on examination.

LD50 (Servon XRK 60) = 3.20 mL/kg bw. or 3.68 g/kg bw (TS specific gravity 1.15)

Equivalent to an LD50  for 100% CHPTAC of 2213 mg/kg bw/day

Interpretation of results:
GHS criteria not met
Conclusions:
A reliable study conducted very largely in compliance with a standard guideline but without GLP, identified an LD50 value for 60% CHPTAC of 3.20 mL/kg bw in male and female rats. This would be equivalent to an LD50 for 100% CHPTAC of 2213 mg/kg bw.
Executive summary:

In an acute toxicity study, the toxic potential of CHPTAC was tested dermally on male and female rats. A LD 50 value for 60% CHPTAC of 3.20 mL/kg bw was identified in male and female rats. This would be equivalent to an LD50 for 100% CHPTAC of 2213 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 213 mg/kg bw
Quality of whole database:
Study conducted similar to guideline

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study witha acceptable restrictions.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2 mLkg bw 65% CHPTAC (1174 mg/mL for 65% CHPTAC) = 2348 mg/kg bw
No. of animals per sex per dose:
5
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 348 mg/kg bw
Remarks on result:
other: 65% CHPTAC
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 526 mg/kg bw
Remarks on result:
other: for 100% CHPTAC (according to RAR, 2008).
Interpretation of results:
study cannot be used for classification
Conclusions:
The dermal LD50 value was found to be greater than 2348 mg/kg bw which corresponds to 1526 mg/kg of pure CHPTAC.
Executive summary:

A limit test was conducted to assess the dermal toxicity of the test substance (65% CHPTAC). Under the experimental conditions the dermal LD50 value was found to be greater than 2348 mg/kg which corresponds to 1526 mg/kg of pure CHPTAC.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
1 526 mg/kg bw
Quality of whole database:
Guideline study

Additional information

ORAL

The key oral study was chosen from 4 studies of reliability 2 (reliable with restrictions) as the most recent of those for which sufficient data were available for review during entry to IUCLID5. Findings from the remaining three studies supported those of the key study. Where adequate data were available the LD50 values for pure CHPTAC were in every case greater than 2000 mg/kg bw/day. For a further two studies (reliability 4) an LD50 of >2000 mg/kg bw/day was also given, apparently in relation to an aqueous solution of CHPTAC, giving a conversion to an LD50 lower than 2000 mg/kg bw/day for the pure substance. However, sufficient details were not available during entry to IUCLID5 for this to be reliably ascertained.

The study selected by FIN to provide the LD50 used in risk characterization (Kynoch et al., 1982/Dynamit Nobel, 1982) was not available during entry to IUCLID5. The LD50 value identified in this study is very similar to that of the key study.

 

 

DERMAL

The key dermal study was chosen from two very similar studies in the rat. The findings of the supporting study confirm those of the key study.

Justification for classification or non-classification

Based on the available data, classification via the oral route is not required (Regulation (EC) No 1272/2008; Directive 67/548/EEC).

The studies identified do not indicate classification via the dermal route for the test material (Regulation (EC) No. 1272/2008; Directive 67/548/EEC). However, conversion to account for the concentration of CHPTAC in the test material means that the tested dose of pure CHPTAC was slightly lower than the upper value (2000 mg/kg bw) above which classification would not be required.