m-cresol

Long-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

long-term toxicity to aquatic invertebrates

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across approach should be used to support the assessment of m-cresol (3-methylphenol) and for data gap filling using ecotoxicity data of p-cresol (4-methylphenol). Together with the o-cresol (2-methylphenol), they make up the structural isomers of methylated phenol. The different substitution patterns lead to minor differences in chemical reactivity of the substances. It is reasonable to assume and experimentally verified that both compounds have nearly identical behavior in physico-chemical, environmental fate and (eco-)toxicological studies. Studies regarding o-cresol 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-cresol is slightly more toxic 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)
The source substance, p-cresol is a mono-constituent with typical concentration of 99.5 % (range 98.0 – 99.8 %). The main impurities in p-cresol are m-cresol, with a typical concentration of 0.2 % (0.1 – 0.4 % range allowed), and o-cresol, with a typical concentration of 0.15 % (0.05 – 0.8 % range allowed). This source substance may contain up to 0.15 % phenol, C6H6O, CAS No. 108-95-2, EC No. 203-632-7 (0.05 – 0.8 % range allowed).
The second substance, o-cresol, is a mono-constituent with typical concentration of 99.5 % (range 99.4 – 99.8 %). The main impurities in o-cresol are phenol, C6H6O, CAS No. 108-95-2, EC No. 203-632-7 with a typical concentration of 0.25 % (up tp 0.5 % acceptable) and m-cresol, with a typical concentration of 0.03 % (0.03 – 0.05 % range allowed). Furthermore, up to 0.05 % p-cresol, with a typical concentration of 0.04 % may be present.
The target substance, m-cresol is a mono-constituent with a typical concentration of 99.2 % (range 98.0 – 99.8 %). The main impurity in m-cresol is p-cresol, with a typical concentration of 0.6 % (0.2 – 1.2 % range allowed). The target substance also may contain up to 0.2 % (0.05 – 0.8 % range allowed) 2-tert-butyl-5-methylphenol, C11H16O, CAS No. 88-60-8, EC No. 201-842-3.

All substances are structural isomers of methylated phenol. The structures consist of a benzene ring, a methyl group and an hydroxyl group, substituted directly to the ring. They have a clear identity and are of high purity ( > 99 %).

3. ANALOGUE APPROACH JUSTIFICATION
As expected due to the structural similarities between source and target substances the comparison of various physico-chemical parameters demonstrate a high level of consistency. Only slight differences, e.g. melting point exist due to symmetry reasons. It is known, that different isomers establish a different reactivity towards nucleophilic addition and substitution of the benzene ring due to the difference in M- and I-effect in the different positions, i.e.: meta-, ortho- or para- substitution pattern. Of particular importance to environmental effects are the values for partition coefficient
(log Kow), vapour pressure, water solubility and dissociation constant. All substances have medium vapour pressures and thus they are considered as low volatile. Based upon their logKoc values, the substances have a low potential for adsorption. The experimentally determined logKow values are all within the same range and very low. This supports this consideration that the substances have a low potential for bioaccumulation. The pKa values are in range of 10.09 – 10.29, which indicates that at environmentally relevant pH values (5 – 9) the substances are largely non-dissociated. The values of the isomers are very close together, resulting in the same environmental fate and ecotoxicity. Moreover, the substances will be stable towards hydrolysis under these conditions. As water solubility and short term toxicological effects towards aquatic species are known and comparable, it is reasonable to assume, that the long-term behavior of the target substance will also be comparable to source substance.

Concerning toxicity towards activated sludge, p-cresol is slightly more toxic than m-cresol, while m-cresol shows the highest toxicity regarding nitrification. Therefore, the source and target substances can be regarded to show comparable effects. The source substance has been identified to be quantitatively slightly more toxic towards microorganisms in general than the target substance. The analogue-approach was used for this read across because of the above-mentioned structural, chemical and (eco-)toxicological similarities between p-cresol and m-cresol taking into account the comprehensive database. Finally, the reliable p-cresol studies cover the data gaps identified for m-cresol.

4. DATA MATRIX

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Preliminary guideline proposal of the German Umweltbundesamt, state 1984-01-01

Deviations:

no

GLP compliance:

not specified

Analytical monitoring:

yes

Vehicle:

no

Test organisms (species):

Daphnia magna

Details on test organisms:

IRCHA strain - Age: 24 h

Test type:

semi-static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

21 d

Hardness:

2.5 mmol/l Ca + Mg
synthetic fresh water

Test temperature:

25 +/- 1 °C

pH:

8.0 +/- 0.2
pH values were measured during the test in two tests-vessels per concentration level. The detected variation of the parameter had
no negative influence on the organisms.

Dissolved oxygen:

oxygen-concentrations were measured during the test in two tests-vessels per concentration level. The detected variation of the parameter had
no negative influence on the organisms.

Salinity:

Na/K ratio: 10:1

Details on test conditions:

- Tested concentration range: 0.003-10 mg/L
Determination of NOEC for reproduction rate, parent mortality, and
the time of the first appearance of offspring - Number of replicates: 4 - individuals per replicate: 20

Reference substance (positive control):

yes

Remarks:

chromate

Duration:

21 d

Dose descriptor:

NOEC

Effect conc.:

1 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mortality

Details on results:

the most sensitve parameter (of parent animal pmortality, reporduction rate, and appearance of first offspring) was used for NOEC determination

- Only the nominal value for the most sensitive parameter is given. However, no losses were reported to be greater than 20%.
- Tested concentration range: 0.003-10 mg/L

Validity criteria fulfilled:

not specified

Conclusions:

The long-term toxicity of p-cresol to aquatic invertebrates was determined by a test according to the preliminary guideline proposal of the German Umweltbundesamt from1984. The 21d-NOEC is 1 mg/L.

Executive summary:

The long-term toxicity of p-cresol to aquatic invertebrates was determined by a test according to the preliminary guideline proposal of the German Umweltbundesamt from1984. The 21d-NOEC is 1 mg/L.

Description of key information

No data on chronic toxicity towards aquatic invertebrates are available for o-cresol and therefore, a read-across from p-cresol is applied. The long-term toxicity of p-cresol to aquatic invertebrates was determined in a semi-static test according to the preliminary guideline proposal of the German Umweltbundesamt from1984. After 21 days of exposure a NOEC of 1 mg/l was determined.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

NOEC

Effect concentration:

1 mg/L

Additional information

There is no study on chronic toxicity towards aquatic invertebrates available using m-cresol as test substance.

In order to get a comprehensive data set for m-cresol a read-across from p-cresol is applied, in accordance with the following justification:

Justification for the read-across approach:

Data from substances who’s physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be used in a read-across approach in order to avoid unnecessary animal testing. It can be stated that the 3 cresols act as a prime example of substances that are suitable for read-across. Cresols are isomers and, thus ideally fulfill the recommended criteria of structural similarity. In its chemical structure, a cresol molecule has a methyl group substituted onto the benzene ring of a phenol molecule, by different arrangement of the -CH3 groups are three structural isomers possible. (ortho-cresol, meta-cresol and para-cresol). Of particular importance to environmental effects are the values for partition coefficient (log Kow), vapour pressure, water solubility and dissociation constant. The values of the isomers are very close together, resulting in the same environmental fate and behaviour. Further, with regard to the bioderadation behavior, all 3 cresols are readily biodegradable. Concerning aquatic toxicity of the cresols on aquatic species, a large number of experimental results from tests with fish, invertebrates and algae are available, indicating a similar toxicity of all isomers, with p-cresol being slightly more toxic in acute tests: Based on the similarities in the results mentioned above the read-across approach is therefore scientifically justified.

The study resulting in the most sensitive NOEC ist used for read-across.