Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The oral LD50 is > 2000 mg/kg bw in rats.

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:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Guideline study under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
minor, not affecting the outcome. Clinical observations made at 4 hours 30 minutes rather than 4 hours after dosing in Step 2. Food replaced in cages at 4 hours 30 minutes rather than at 4 hours, in Step 2.
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
minor, not affecting the outcome. Clinical observations made at 4 hours 30 minutes rather than 4 hours after dosing in Step 2. Food replaced in cages at 4 hours 30 minutes rather than at 4 hours, in Step 2.
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories S.r.l.
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: SPF
- Age at study initiation: 6-7 weeks
- Weight at study initiation:157-165g
- Housing:
- Diet (e.g. ad libitum): ad libitum, ssniff SM
- Water (e.g. ad libitum): ad libitum, municipal water supply
- Acclimation period: 5 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 55-57
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: To:TEST ANIMALS
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Doses:
One dose of 2000 mg/kg body weight was given only once on day 1.
No. of animals per sex per dose:
6 individual female rats were all given the same dose of 2000 mg/kg of body weight.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations made twice daily. Weights measured at allocation, on the day of dosing and on days 2, 8 and 15.
- Necropsy of survivors performed: yes, on all animals.
- Other examinations performed: no histopathology
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality at the limit dose of 2000 mg/kg bw
Clinical signs:
other: No clinical signs noted
Gross pathology:
No pathology noted

No mortality occurred and no clinical signs were observed in the first group of animals initially dosed at 2000 mg/kg (Group 2, Step 1) and in the further group of 3 females dosed at the same dose level (Group 4, Step 2).

The results indicate that ZWA 5496/100 did not induce toxic effects in any of the rats following oral administration.

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity of the test material is low, with a LD50 greater than 2000 mg/kg body weight. The substance is not classified according to Regulation EC No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
adequate

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Justification for type of information:
The study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size [exposure considerations]. Furthermore, according to Annex VIII, Section 8.5, Column 2, of Regulation EC No. 1907/2006, a toxicity study, in addition to the acute oral toxicity study, under 8.5.2 to 8.5.3 shall be provided for at least one other route. Regulation EC No. 863/2016 amends this data requirement, stating that substances that are not toxic via the oral route may be expected with high certainty to be also non-toxic via the dermal route. The risk of acute toxicity by the dermal route has been addressed in light of an acute oral toxicity study with a LD50 > 2000 and no systemic toxicity observed in other in vivo studies. It is determined that testing for acute dermal toxicity is not scientifically indicated. The criteria for satisfaction of Sections 8.5.2 and 8.5.3 are met and the data requirement for an acute toxicity study by a third route, inhalation, is waived.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
According to Regulation EC No. 863/2016 amending Regulation EC No. 1907/2006, acute testing by the dermal route does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route, and no systemic effects have been observed in in vivo studies with dermal exposure. The test material displayed an acute oral LD50 > 2000 mg/kg bw in rats, is not classified as STOT SE, and no systemic toxicity or local irritation was observed in a LLNA study in mice. Therefore the substance meets the criteria for waiving the testing requirements for acute dermal toxicity.
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute inhalation toxicity study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Furthermore, according to Commission Regulation (EU) 2016/863 amending Regulation EC No. 1907/2006, acute dermal toxicity testing does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route, and no systemic effects have been observed in in vivo studies with dermal exposure. The test material displayed an acute oral LD50 > 2000 mg/kg bw in rats, no evidence of systemic toxicity in a repeated dose toxicity study, and is not classified as STOT SE. The study for acute inhalation toxicity is not required, as the acute toxicity of two routes of administration have been addressed, as required by Regulation EC No. 1907/2006, Annex VIII.

Justification for classification or non-classification

The oral LD50 of the substance is > 2000 mg/kg bw in female Wistar rats, and hence is not classified. No study for dermal toxicity was undertaken based on Commission Regulation (EU) 2016/863. No systemic toxicity was observed in a dermal LLNA study of the substance, nor was there systemic toxicity observed in a 28-day repeated dose and reproductive toxicity screening test. The criteria for classification for acute toxicity in Regulation EC No. 1272/2008 is not met and the substance is not classified.