Registration Dossier

Administrative data

Description of key information

Oral and inhalation acute toxicity are all considered.

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:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: General overview of study results is presented, in accordance with EPA reporting rule on certain pesticide inert ingredients. No specific methodology is detailed.
Qualifier:
according to
Guideline:
other: Section 8 (d) of the Toxic Substances Control Act (Fed. Vol. 54, No. 38, Tuesday, February 28, 1989)
Deviations:
not specified
Principles of method if other than guideline:
EPA reporting rule on certain pesticide inert ingredients. No specific methodology is detailed.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
Not specified
Doses:
Not specified
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Details on study design:
Not specified
Statistics:
Not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 1 000 other: mg/kg
Based on:
not specified
Mortality:
No deaths
Clinical signs:
Not specified
Body weight:
Not specified
Gross pathology:
Not specified
Other findings:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 1000 mg/kg. It should be noted that this study could be waived as it is not relevant to the expected exposure to the substance. This is in accordance with Annex VII, Section 8.5.1 which states that
8.5.1. By oral route - The study need not be conducted if a study on acute toxicity by the inhalation route (8.5.2) is available.”
However, this study is included as supporting information to fulfil this data endpoint.
Although a limit test at > 1000 mg/kg no classification is proposed for oral toxicity, as this route of exposure is not anticipated.
Executive summary:

LD50 > 1000 mg/kg. It should be noted that this study could be waived as it is not relevant to the expected exposure to the substance. This is in accordance with Annex VII, Section 8.5.1 which states that:

8.5.1. By oral route - The study need not be conducted if a study on acute toxicity by the inhalation route (8.5.2) is available.”

However, this study is included as supporting information to fulfil this data endpoint.

Although a limit test at > 1000 mg/kg no classification is proposed for oral toxicity, as this route of exposure is not anticipated.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw
Quality of whole database:
No specific methods are provided, and this study could be waived in accordance with Annex VII, Section 8.5.1 which states that
8.5.1. By oral route - The study need not be conducted if a study on acute toxicity by the inhalation route (8.5.2) is available.
Although a limit test at > 1000 mg/kg no classification is proposed for oral toxicity, as this route of exposure is not anticipated.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: General overview of study results is presented, in accordance with EPA reporting rule on certain pesticide inert ingredients. No specific methodology is reported.
Qualifier:
according to
Guideline:
other: Section 8 (d) of the Toxic Substances Control Act (Fed. Vol. 54, No. 38, Tuesday, February 28, 1989)
Deviations:
not specified
Principles of method if other than guideline:
EPA reporting rule on certain pesticide inert ingredients. No specific methodology is reported.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
other: species not specified.
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Details on inhalation exposure:
Not specified
Analytical verification of test atmosphere concentrations:
not specified
Remarks on duration:
Not specified
Concentrations:
Not specified
No. of animals per sex per dose:
Not specified
Control animals:
not specified
Details on study design:
Not specified
Statistics:
Not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
> 800 000 ppm
Based on:
not specified
Sex:
not specified
Dose descriptor:
LC50
Effect level:
3 956 155.4 mg/m³ air
Based on:
not specified
Remarks on result:
other: Conversion based on ACGIH ("2010 TLVs and BEIs, Based on the Documentation of the Threshold LImit Values for Chemical Substances and Physical Agents & Biological Exposure Indices")
Mortality:
No deaths
Clinical signs:
other: Not specified
Body weight:
Not specified
Gross pathology:
Not specified
Other findings:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LC50 > 800,000 ppm. Although limited, the data set in the report indicates that the substance is not acutely harmful by inhalation exposure, and supports the weight of evidence approach for the substance. This matches the experience of handling and use of the substance. The substance is not deemed to be classified on the basis of inhalation toxicity.
Executive summary:

LC50 > 800,000 ppm (equates to 3956155.419 mg/m3). Although limited, the data set in the report indicates that the substance is not acutely harmful by inhalation exposure, and supports the weight of evidence approach for the substance. This matches the experience of handling and use of the substance. The substance is not deemed to be classified on the basis of inhalation toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
989 038 mg/m³
Quality of whole database:
The literature data provides endpoints for a number of mammalian species, and is considered appropriate for use in the scope of a weight of evidence approach. Although exposures are for 30 minutes only, the report indicates that there were no effects at the highest dose tested.

Review of the EU legislation does not provide for conversion from 30 min LC50 exposure values. Regulation (EC) No 1272/2008 on classification, labelling and packaging (the CLP regulation), Part 3: Health Hazards, section 3.1.2. Criteria for classification of substances as acutely toxic part b provides for scaling of generic concentrations at 1 hour to a 4-hour LC50 as follows:

(b) Generic concentration limits for inhalation toxicity in the table are based on 4 hour testing exposures. Conversion of existing inhalation toxicity data which have been generated using a 1 hour exposure can be carried out by dividing by a factor of 2 for gases and vapours and 4 for dusts and mists.

In the absence of guidance for converting from 30 minutes, the above is taken and a factor of 4 (for gases) is applied to gain an LC50 at 4 hours for the substance. This is a conservative estimate. This yields the following results:

rat: inhalation LC50: >200,000 ppm, = >200,000 mg/l = >0.989e+6 mg/m3
This is still far above the threshold for classification as harmful by inhalation. No classification is applicable.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Data is available on the above endpoints and gave the following results:

 

Acute toxicity: Oral.

 

Two studies are available for review, each giving the endpoint as:

-         LD50: >1000 mg/kg

 

These studies in this section could be waived as these are not relevant to the expected exposure to the substance. This is in accordance with Annex VII:

 

“In accordance with 8.5.1. By oral route - The study need not be conducted if a study on acute toxicity by the inhalation route (8.5.2) is available.”

 

However, it is deemed appropriate to include these for completeness purposes. No classification is proposed for this endpoint, as the LD50 studies indicated that no toxicity is observed via the oral route.

 

Acute toxicity: Dermal.

This study is waived, on the basis that the route of exposure is not applicable as the substance is a gas.

 

Acute toxicity: Inhalation.

 

There is a number of literature data endpoints for mammalian species, and is considered appropriate for use in the scope of a weight of evidence approach. Although exposures are for 30 minutes only, the report indicates that there were no effects at the highest dose tested. 

 

Review of the EU legislation does not provide for conversion from 30 min LC50 exposure values. Regulation (EC) No 1272/2008 on classification, labelling and packaging (the CLP regulation),Part 3: Health Hazards, section 3.1.2.Criteria for classification of substances as acutely toxic part b provides for scaling of generic concentrations at 1 hour to a 4-hour LC50 as follows:

 

(b) Generic concentration limits for inhalation toxicity in the table are based on 4 hour testing exposures. Conversion of existing inhalation toxicity data which have been generated using a 1 hour exposure can be carried out by dividing by a factor of 2 for gases and vapours and 4 for dusts and mists.

 

In the absence of guidance for converting from 30 minutes, the above is taken and a factor of 4 (for gases) is applied to gain an LC50 at 4 hours for the substance. This is a conservative estimate. This yields the following results:

 

mouse: inhalation LC50: 190,000 ppm, = 0.939e+6 mg/m3

guinea pig: inhalation LC50: >200,000 ppm, = >0.989e+6 mg/m3

rabbit: inhalation LC50: >200,000 ppm, = >0.989e+6 mg/m3

rat: inhalation LC50: >200,000 ppm, = >0.989e+6 mg/m3

This is still far above the threshold for classification as harmful by inhalation. No classification is applicable.


Justification for selection of acute toxicity – oral endpoint
Study results rather than a literature based result.

Justification for selection of acute toxicity – inhalation endpoint
Study results rather than a literature based result.

Justification for selection of acute toxicity – dermal endpoint
The substance is a gas, and hence exposure by the dermal route is precluded as the inhalation route is the most likely route of exposure. The substance is proposed to not be dermally toxic.

Justification for classification or non-classification

The above studies have all been ranked reliability 2 according to the Klimish et al system. This ranking was deemed appropriate because the studies were not conducted to GLP and are not in compliance with agreed protocols. However, sufficient dose ranges and numbers are detailed and the results are comparable with each other. As such, it is deemed appropriate to apply a weight of evidence approach based on similarity and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). No classification for acute effects is therefore required.