Registration Dossier

Administrative data

Description of key information

An acute oral toxicity study has been conducted on test item tetramethrin according to OECD guideline no. 423.

The acute oral LD50 of Tetramethrin Tech. Grade in Wistar rats is more than 2000 mg/kg body weight

An acute inhalation toxicity study has been conducted on test item tetramethrin according to OECD guideline no. 403.

The acute inhalation (4 hours) LC50 value of tetramethrin is more than 5.63 mg/l (maximum attainable concentration) of chamber air.

An acute dermal toxicity study has been conducted on test item tetramethrin according to OECD guideline no. 402 and EPA OPPTS 870.1200.

The acute dermal LD50 of tetramethrin tech. grade in Wistar rats is more than 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance is the racemic form of the target substance d-tetramethrin. Tetramethrin does consist of 50% d- and l-form, and both do exist as cis and trans isomers. Hence, the target substance does consist of d-cis-tetramethrin, d-trans-tetramethrin, l-cis-tetramethrin and l-trans-tetramethrin, whereas the target substance only contains the first two (i.e. d-cis-tetramethrin, d-trans-tetramethrin).
Both, the source as well as the target substance, do have a cis/trans ratio of approximately 1/4 and obviously do share same molecular formula and mass, functional groups and other properties. Thus, the source substance by definition does contain ~50% of the d-form and the l-form is not expected to be significantly different with respect to its toxic properties. Acute toxicity has been assessed in an oral, a dermal and an inhalation acute toxicity study to assess acute toxicity to rodents. Accordingly, data do indicate that racemic tetramethrin and thus also d-tetramethrin is not affecting acute rodent toxicity, irrespectively of the route of exposure. The upper limit concentration of 2000 mg/kg bw and 5.63 mg/L (saturated conc. in air) in the studies did not affect mortality or other clinical observations in rat and results of d-tetramethrin are not expected to significantly differ from the racemic mixture, considering that this contained the d-enantiomer as the main component.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The d-tetramethrin with a purity > 80 % does contain its corresponding l-form as an impurity in the range of < 7%, other impurities from the manufacturing process are individually below 1% (w/w) each. The source substance that has been tested was having a purity of approx. 98% as tetramethrin with a cis/trans ratio of 1/4 and a d-form/l-form ratio of ~50/50.
3. ANALOGUE APPROACH JUSTIFICATION
Source and Target substance do share identical structure and molecular weight, only differentiating by the fact that the source substance is a racemic mixture, whereas the target substance represents almost pure d-form. Thus, behaviour regarding toxicity to rodents is expected not being affected significantly by stereochemistry, and being fully comparable, thus justifying using available data on rodent toxicity properties on the racemic form for read-across to the d-enantiomer.
4. DATA MATRIX
Composition comparison
D-tetramethrin (target) tetramethrin (source)
D-trans tetramethrin 70 - 80% 40 – 50%
D-cis tetramethrin 10 - 20% 7 – 11 %
L-trans tetramethrin 0 – 5% 35 – 40%
L-cis tetramethrin 0 – 2% 7 – 11%
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Conclusions:
The acute oral LD50 of racemic tetramethrin in Wistar rats is more than 2000 mg/kg body weight, considered relaible also for the d-entiomer, d-tetramethrin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance is the racemic form of the target substance d-tetramethrin. Tetramethrin does consist of 50% d- and l-form, and both do exist as cis and trans isomers. Hence, the target substance does consist of d-cis-tetramethrin, d-trans-tetramethrin, l-cis-tetramethrin and l-trans-tetramethrin, whereas the target substance only contains the first two (i.e. d-cis-tetramethrin, d-trans-tetramethrin).
Both, the source as well as the target substance, do have a cis/trans ratio of approximately 1/4 and obviously do share same molecular formula and mass, functional groups and other properties. Thus, the source substance by definition does contain ~50% of the d-form and the l-form is not expected to be significantly different with respect to its toxic properties. Acute toxicity has been assessed in an oral, a dermal and an inhalation acute toxicity study to assess acute toxicity to rodents. Accordingly, data do indicate that racemic tetramethrin and thus also d-tetramethrin is not affecting acute rodent toxicity, irrespectively of the route of exposure. The upper limit concentration of 2000 mg/kg bw and 5.63 mg/L (saturated conc. in air) in the studies did not affect mortality or other clinical observations in rat and results of d-tetramethrin are not expected to significantly differ from the racemic mixture, considering that this contained the d-enantiomer as the main component.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The d-tetramethrin with a purity > 80 % does contain its corresponding l-form as an impurity in the range of < 7%, other impurities from the manufacturing process are individually below 1% (w/w) each. The source substance that has been tested was having a purity of approx. 98% as tetramethrin with a cis/trans ratio of 1/4 and a d-form/l-form ratio of ~50/50.
3. ANALOGUE APPROACH JUSTIFICATION
Source and Target substance do share identical structure and molecular weight, only differentiating by the fact that the source substance is a racemic mixture, whereas the target substance represents almost pure d-form. Thus, behaviour regarding toxicity to rodents is expected not being affected significantly by stereochemistry, and being fully comparable, thus justifying using available data on rodent toxicity properties on the racemic form for read-across to the d-enantiomer.
4. DATA MATRIX
Composition comparison
D-tetramethrin (target) tetramethrin (source)
D-trans tetramethrin 70 - 80% 40 – 50%
D-cis tetramethrin 10 - 20% 7 – 11 %
L-trans tetramethrin 0 – 5% 35 – 40%
L-cis tetramethrin 0 – 2% 7 – 11%
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 5.63 mg/L air (analytical)
Based on:
test mat.
95% CL:
>= 4.77 - <= 6.49
Exp. duration:
4 h
Conclusions:
The acute inhalation (4 hours) LC50 value of racemic tetramethrin is greater than 5.63 mg/L aerosol of chamber air. No signs of toxicity were seen and no mortality. The data are considered adequate for d-tetramethrin, also.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
5 630 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance is the racemic form of the target substance d-tetramethrin. Tetramethrin does consist of 50% d- and l-form, and both do exist as cis and trans isomers. Hence, the target substance does consist of d-cis-tetramethrin, d-trans-tetramethrin, l-cis-tetramethrin and l-trans-tetramethrin, whereas the target substance only contains the first two (i.e. d-cis-tetramethrin, d-trans-tetramethrin).
Both, the source as well as the target substance, do have a cis/trans ratio of approximately 1/4 and obviously do share same molecular formula and mass, functional groups and other properties. Thus, the source substance by definition does contain ~50% of the d-form and the l-form is not expected to be significantly different with respect to its toxic properties. Acute toxicity has been assessed in an oral, a dermal and an inhalation acute toxicity study to assess acute toxicity to rodents. Accordingly, data do indicate that racemic tetramethrin and thus also d-tetramethrin is not affecting acute rodent toxicity, irrespectively of the route of exposure. The upper limit concentration of 2000 mg/kg bw and 5.63 mg/L (saturated conc. in air) in the studies did not affect mortality or other clinical observations in rat and results of d-tetramethrin are not expected to significantly differ from the racemic mixture, considering that this contained the d-enantiomer as the main component.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The d-tetramethrin with a purity > 80 % does contain its corresponding l-form as an impurity in the range of < 7%, other impurities from the manufacturing process are individually below 1% (w/w) each. The source substance that has been tested was having a purity of approx. 98% as tetramethrin with a cis/trans ratio of 1/4 and a d-form/l-form ratio of ~50/50.
3. ANALOGUE APPROACH JUSTIFICATION
Source and Target substance do share identical structure and molecular weight, only differentiating by the fact that the source substance is a racemic mixture, whereas the target substance represents almost pure d-form. Thus, behaviour regarding toxicity to rodents is expected not being affected significantly by stereochemistry, and being fully comparable, thus justifying using available data on rodent toxicity properties on the racemic form for read-across to the d-enantiomer.
4. DATA MATRIX
Composition comparison
D-tetramethrin (target) tetramethrin (source)
D-trans tetramethrin 70 - 80% 40 – 50%
D-cis tetramethrin 10 - 20% 7 – 11 %
L-trans tetramethrin 0 – 5% 35 – 40%
L-cis tetramethrin 0 – 2% 7 – 11%
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Conclusions:
The acute dermal minimum lethal dose of racemic tetramethrin in Wistar rats is more than 2000 mg/kg body weight, and this result is also used for the d-enantiomer d-tetramethrin for hazard and risk assessment.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

In acute toxicity studies by oral, dermal, and inhalation exposure, no mortality was seen at 2000 mg/kg bw, 2000 mg/kg bw, and 5.63 mg/L, respectively. Thus, the substance does not require classification for acute toxicity according to CLP (Regulation EC No. 1272/2008).