m-toluidine

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

fish early-life stage toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2005-2006

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Original study report is in Japanese and is not translated into English, but essential data like graphs and tables are given in English.

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across approach should be used to support the assessment of m-toluidine (3-methylaniline, CAS No. 108-44-1, EC No. 203-583-1) and data gap filling using fate and (eco)toxicity data of p-toluidine (4-methylaniline, CAS No. 106-49-3, EC No. 203-403-1). Together with the o-toluidine (2-methylanikline, CAS No. 95-53-4, EC No. 202-429-0), they make up the structural isomers of methylated aniline. The different substitution pattern lead to minor difference in chemical reactivity of the substances.
It is reasonable to assume and experimentally verified that source and target substance have nearly identical behavior in physico-chemical and (eco) toxicological studies. Studies regarding o-toluidine allow a comprehensive data evaluation, supporting the read-across approach and clarifying the quantitatively similar effects of the substances. While all three isomers exhibit effects in the same range, no clear tendency can be derived. However, in some effects, p-toluidine is slightly stronger than the other isomers. Therefore, the read-across also considers the worst-case approach.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
All substances are structural isomers of methylated aniline. The structures consist of a benzene ring, a methyl group and an amino group, substituted directly to the ring. They have a clear identity with high purity ( > 99 %). (see Justification Document for Details.)

3. ANALOGUE APPROACH JUSTIFICATION
Source and target substances are isomers of methylated aniline. The structures consist of a benzene ring, a methyl group and an amino group, connected directly to the benzene ring. All isomers employ the same empirical formula: C7H9N, and molecular weight: 107.1531 g/mol. A methyl group is substituted either in meta- or in ortho- or para- position to the amino group of the aniline ring. Source and target substances are isomers and therefore have very similar chemical structures and can be regarded as homologous structures. The only difference between both substances is displayed by the position of the methyl group. In addition to only little differences in structure between these substances, there are further data, which confirm the similarity concerning behavior. Due to the common structural aspects, the main physico-chemical parameters like vapour pressure, water solubility, octanol/water partition coefficient, organic carbon partition coefficient and dissociation constant are in the same range.For m-toluidine and p-toluidine, the main ecotoxicological parameters like short-term toxicity on Daphnia and fish, toxicity on algae, and long-term toxicity on Daphnia are in the same range. It is shown that Daphnia is the most sensitive aquatic organism for both isomers.
Overall, based on the comparable composition of source and target, their similar physico-chemical properties and ecotoxicological effects the read-across approach for assessment of the boiconcentration factor and the long-term toxicity towards fish is justified.


For Additional Data confere to the RAAFJustification Document.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

after 0, 7, 14, 21, 28 and 35 days

Vehicle:

not specified

Test organisms (species):

Oryzias latipes

Test type:

other: No information available, but it is assumed that test was carried out under flow-through conditions.

Water media type:

freshwater

Limit test:

no

Total exposure duration:

35 d

Hardness:

21.8-41.3 mg/L as CaCO3

Test temperature:

23.9 +/- 1 °C

pH:

pH 7.1-7.9

Dissolved oxygen:

between 8.39-8.11 mg/L

Nominal and measured concentrations:

Nominal: control, 0.625, 1.25, 2.50, 5.00 and 10.0 mg/L
arithmetic mean: 0, 0.598, 1.18, 2.47, 4.99 and 9.93 mg/L
Recovery > 94%.

Reference substance (positive control):

no

Duration:

35 d

Dose descriptor:

LOEC

Effect conc.:

1.18 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Duration:

35 d

Dose descriptor:

NOEC

Effect conc.:

0.598 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

length

Details on results:

- Survival rate after hatching: in control: 96.5 +/- 4.0%; significant different (p<0.05) with 62.1 +/- 6.3% at 9.93 mg/L (measured concentration) p-toluidine

- Days to hatch or time to release of young: Control: 9.09 +/- 0.07 days; no significant differnces for test solutions with p-toluidine

- Observations on weight of exposed fish surviving at the end of the experiment: control: 63.3 +/- 16.3 mg body weight; significant different (p<0.01) from control with 45.7 +/- 13.2 mg body weight at 4.99 mg/L (measured concentration) p-toluidine

- Observations on body length of fish surviving at the end of the experiment: control: 1.65 +/- 0.15 cm lenght; significant different (p<0.01) from control with 1.45 +/- 0.10 cm lenght at 1.18 mg/L (measured concentration) p-toluidine

- Type of and number with morphological abnormalities: none

- Toxic symptom observed in embryo: none

- Type of and number with behavioural abnormalities after hatching: some fish showed complete loss of equilibrium, lethargic, reduced activity or reduced feeding activity. These effects were not in correlation with concentration of p-toluidine.

The most sensitive endpoint was body length, followed by body weight. Significant differences from control were also observed for the endpoint survival rate at the end of the exposure after hatching.

The study was conducted with 4 replicates each with 15 animals per concentration.

Validity criteria fulfilled:

yes

Remarks:

All validity criteria cannot be assessed sufficiently. Nevertheless the test is considered as valid based on the data given.

Conclusions:

35d-NOEC of p-toluidine on Oryzias latipes of 0.598 mg/L and 35d-LOEC of 1.18 mg/L was determined based on length.

Executive summary:

As there is no data available for m-toluidine, read across with p-toluidine (CAS No. 106-49-0) is proposed to cover this endpoint. m-Toluidine and p-toluidine are isomers and have very similar chemical structures. Their main physico-chemical parameters (vapour pressure, water solubility, octanol/water partition coefficient, organic carbon partition coefficient and dissociation constant) are in the same range. The main ecotoxicological parameters like short-term toxicity on Daphnia and fish, toxicity on algae, and long-term toxicity on Daphnia are also in the same range. It is shown that Daphnia is the most sensitive aquatic organism for both isomers. Therefore a read across between these two substances to cover physico-chemical and ecotoxicological endpoints for m-toluidine seems to be justified. More details regarding the read across justification are depicted in the annex of the Chemical Safety Report (CSR).

Concerning long-term toxicity to fish, a test was conducted to the OECD Guideline 210 (Fish, early-life stage toxicity test) ) by EA, Japan: "Investigation of the Ecotoxicological Effects of OECD High Production Volume Chemicals", Office of Health Studies, Environmental Health Department, Environment Agency, Japan, using p-toluidine as test substance. A 35d-NOEC of p-toluidine on Oryzias latipes of 0.598 mg/L and 35d-LOEC of 1.18 mg/L was determined. The result is based on length as most sensitive endpoint. The values refer to measured concentration of p-toluidine (arithmetic mean) as an analytical monitoring of p-toluidine was performed with HPLC as analytical technique. The measured recovery in test solution was >94%. The hatchability, days to hatch, morphological abnormality rate in embryo, survival rate after hatching, body weight of fish at the end of the exposure, body length of fish surviving at the end of the exposure, toxic symptoms observed in embryo and toxic symptoms observed after hatching were monitored.

Description of key information

For p-toluidine the structural analogue of m-toluidine a LOEC of 1.18 mg/L and a NOEC of 0.598 mg/L were obtained in a Fish, Early-Life Stage Toxicity Test.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

0.598 mg/L

Additional information

As there is no data available for m-toluidine, read across with p-toluidine (CAS No. 106-49-0) is proposed to cover this endpoint. m-Toluidine and p-toluidine are isomers and have very similar chemical structures. Their main physico-chemical parameters (vapour pressure, water solubility, octanol/water partition coefficient, organic carbon partition coefficient and dissociation constant) are in the same range. The main ecotoxicological parameters like short-term toxicity on Daphnia and fish, toxicity on algae, and long-term toxicity on Daphnia are also in the same range. It is shown that Daphnia is the most sensitive aquatic organism for both isomers. Therefore a read across between these two substances to cover physico-chemical and ecotoxicological endpoints for m-toluidine seems to be justified. More details regarding the read across justification are depicted in the annex of the Chemical Safety Report (CSR).

Concerning lon-term toxicity to fish, a test was conducted to the OECD Guideline 210 (Fish, early-life stage toxicity test) ) by EA, Japan: "Investigation of the Ecotoxicological Effects of OECD High Production Volume Chemicals", Office of Health Studies, Environmental Health Department, Environment Agency, Japan, using p-toluidine as test substance.

A 35d-NOEC of p-toluidine on Oryzias latipes of 0.598 mg/L and 35d-LOEC of 1.18 mg/L was determined. The result is based on length as most sensitive endpoint. The values refer to measured concentration of p-toluidine (arithmetic mean) as an analytical monitoring of p-toluidine was performed with HPLC as analytical technique. The measured recovery in test solution was >94%. The hatchability, days to hatch, morphological abnormality rate in embryo, survival rate after hatching, body weight of fish at the end of the exposure, body length of fish surviving at the end of the exposure, toxic symptoms observed in embryo and toxic symptoms observed after hatching were monitored.

This data is not presented in OECD SIDS since it was not available at that time.