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Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
toxicity to reproduction
Remarks:
other: read-across from two and three generation studies
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The analogue CAS No. 128-37-0 (BHT) which shares the same functional groups with the two main constituents of the substance Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 128 -37-0 can be used for the read-across approach.
Principles of method if other than guideline:
Read-across from experimental data on an analogue.
GLP compliance:
no
Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: Generation not specified (migrated information)
Reproductive effects observed:
not specified

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) with the two main constituents of the substance Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 128 -37-0 can be used for the read-across approach. The properties are as follows:

  

- a log Pow value which is 4.9 for the Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol and 5.2 for 2,6-di-tert-butyl-4-methylphenol (BHT) and

 

- a low water solubility which is 0.4 ± 0.3 mg/L at 20 ºC for the Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol and 0.4-0.6 mg/L at 20-25 ºC for 2,6-di-tert-butyl-4-methylphenol (BHT)

 

DATA MATRIX read- across (any other information on results, including tables)

 

 

CAS Number

 

Source chemical

128-37-0

Target chemical

 

CHEMICAL NAME

 

2,6-di-tert-butyl-4-methylphenol

Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol

PHYSICO-CHEMICAL DATA

 

Melting Point

Experimental results:

69.8 - 71 ºC

Experimental results:

-36.3 ºC to -28.2 ºC

 

Boiling Point

Experimental results:

265 ºC

Experimental results:

253.9 ºC

 

pKa

Experimental results:

pKa = 12.2

Experimental results:

Read-across from

2,6-di-tert-butylphenol:

pKa = 11.7 at 25 ºC

 

Read-across from

2,4,6-tri-tert-butylphenol:

pKa = 12.2 at 25 ºC

 

Partition Coefficient

(log Kow)

Experimental results:

Log Pow = 5.2

Experimental results:

log Pow = 4.9

 

Water solubility

 

Experimental results:

0.4 -0.6 mg/l at 20-25 ºC

 

Experimental results:

0.4 ± 0.3 mg/l at 20 ºC

Vapour pressure

Experimental data:

3.82 Pa at 24.85 ºC

Experimental results:

310 Pa at 20 ºC (2.33 mm Hg)

 

ENVIRONMENTAL FATE and PATHWAY

 

Aerobic Biodegradation

 

Estimated data:

Not readily biodegradable 

 

Experimental results:

Not readily biodegradable 

 

ENVIRONMENTAL TOXICITY

 

Acute Toxicity to Fish

Estimated data: ECOSAR

LC50 (96 h) = 0.2 mg/l

Experimental data: Key study:

LC50 (96 h)=0.31mg/L

Acute Toxicity to Aquatic Invertebrates

Experimental data:

EC50 (48 h) =0.48mg/L

Experimental data:

Key study in Daphnia magna:

48h-EC50= 0.4 mg/L

 

Toxicity to Aquatic algae and cyanobacteria

 

Estimated data: ECOSAR

EC50 (96 h) = 0.76 mg/L

Experimental data: 

Key study:

EC50 (72 H) = 3 mg/L

NOEC = 1.6 mg/L

 

 

MAMMALIAN TOXICITY

 

Acute Toxicity: Oral

Experimental data:

Key study: LD50 >6000 mg/kg bw (rats)

 

Experimental data:

Key study: LD50 = 2976 mg/kg bw (rats)

 

 

 

Acute Toxicity: Dermal

Experimental data:

Key study:

LD50 > 2000 mg/kg bw (rats)

 

Experimental data:

Key study:

LD50 > 2000 mg/kg bw (rats)

 

Skin and eye irritation.

Skin sensitisation.

Experimental data:

Key study:

Not a skin irritant.

 

Not an eye irritant.

 

Not a skin sensitizer.

 

Experimental data:

Key studies:

Not a skin irritant.

 

Eye damage Category 1

 

Not a skin sensitizer.

Repeated Dose Toxicity

Experimental results: Weight of evidence:

NOAEL from chronic study: 25 mg/kg bw/day

 

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

NOAEL from chronic study: 25 mg/kg bw/day

 

Genetic Toxicity in vitro

 

Gene mutation in bacteria

Experimental results: Weight of evidence:

Negative

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

Negative

 

Chromosomal aberrations

Experimental results: Weight of evidence:

Negative

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

Negative

 

Gene mutation in mammalian cells

Experimental results: Weight of evidence:

Negative

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

Negative

 

Genetic Toxicity in vivo

 

Experimental results: Weight of evidence:

Negative

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

Negative

 

Carcinogenicity

Experimental results: Weight of evidence:

Not classified as carcinogenic.

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

Not classified as carcinogenic.

 

Toxicity to reproduction

 

Experimental results: Weight of evidence:

 

Effects on fertility: 

The NOAEL was 25 mg/kg bw/day in the rat.

 

Developmental toxicity:

No data

 

Experimental results: Weight of evidence: Read-across from 2,6-di-tert-butyl-4-methylphenol (BHT)

Effects on fertility:

The NOAEL was 25 mg/kg bw/day in the rat.

 

Developmental toxicity: 

No data

 

Conclusions:
Based on experimental data, the read-across approach is applied and the NOAEL for effects on fertility is 25 mg/kg bw/day.
Executive summary:

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) with the two main constituents of the substance Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 128 -37-0 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the NOAEL for effects on fertility is 25 mg/kg bw/day.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
25 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Weight of evidence: Based on experimental data, the read-across approach is applied and the NOAEL for effects on fertility is 25 mg/kg bw/day.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Weight of evidence:

The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) with the two main constituents of the substance Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 128 -37-0 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the NOAEL for effects on fertility is 25 mg/kg bw/day.


Short description of key information:
Weight of evidence: Based on experimental data, the read-across approach is applied and the NOAEL for effects on fertility is 25 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:
Weight of evidence:
The analogue CAS No. 128-37-0 (BHT) which shares the same functional group (alkylphenol) with the two main constituents of the substance Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 128 -37-0 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the NOAEL for effects on fertility is 25 mg/kg bw/day.

Effects on developmental toxicity

Description of key information
Key study:Based on experimental data, the read-across approach is applied and the NOAEL for maternal toxicity is 93.5 mg/kg bw/day and the NOAEL for developmental toxicity is 375 mg/kg bw/day (the highest dose tested). 
 
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test method similar to OECD 414.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
Principles of method if other than guideline:
2,2´-methylenebis (4-methyl-6-tert-butylphenol) was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 93.5, 187 or 375 mg/kg bw during days 7 to 17 of pregnancy and the effects of the compound on dams and fetal developments were examined.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Route of administration:
oral: gavage
Details on exposure:
- Vehicle: yes
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
From day 7 to 17 of pregnancy
Frequency of treatment:
Daily
Remarks:
Doses / Concentrations:
0, 93.5, 187 and 375 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
20 to 24 pregnant rats for each group
Control animals:
yes, concurrent vehicle
Maternal examinations:
Body weight and mortality
Ovaries and uterine content:
All pregnant rats on the 20th day of pregnancy were killed under ether anesthesia. Through an incision to remove the fetuses, the number of corpora lutea, number of implantations, the number of fetal deaths, the number of fetal survival, sex ratio, fetuses body weight and number of death implantations (early, late) were examined.

Fetal examinations:
External malformations. 1/3 of fetal survival was examined for internal organ abnormalities and the remaining 2 / 3 were examined for skeletal abnormalities.
Statistics:
Experimental results are evaluated as a unit matrix, test, t-test or rank sum test and the rate of 5% and 1% risk compared with the level of the control group.
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
In the dams at the two higher doses of 187 and 375 mg/kg, toxic signs such as hair fluffing and diarrhoea were observed, and their body weight gain and food consumption were suppressed. Two dams, which showed marked diarrhoea in the highest dose group, died (Tables available in English in the article).
Dose descriptor:
NOAEL
Effect level:
93.5 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
375 mg/kg bw/day (actual dose received)
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There was no evidence of fetal malformation attributable to treatment with the compound in any of the dose groups treated, although a slight increase in fetal death was found in the highest dose group (Tables available in English in the article).
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
It is concluded that 2,2'-methylenebis (4-methyl-6-tert--butylphenol) has a weak lethal effect on fetal development but not a teratogenic effect in the rat.
Executive summary:

2,2´-methylenebis (4-methyl-6-tert-butylphenol) was given orally to pregnant Wistar rats by stomach intubation at the dose levels of 93.5, 187 or 375 mg/kg bw during days 7 to 17 of pregnancy and the effects of the compound on dams and fetal developments were examined. In the dams at the two higher doses of 187 and 375 mg/kg, toxic signs such as hair fluffing and diarrhoea were observed, and their body weight gain and food consumption were suppressed. Two dams, which showed marked diarrhoea in the highest dose group, died. However, there was no evidence of fetal malformation attributable to treatment with the compound in any of the dose groups treated, although a slight increase in fetal death was found in the highest dose group. It is concluded that 2,2'-methylenebis (4-methyl-6-tert-butylphenol) has a weak lethal effect on fetal development but not a teratogenic effect in the rat. This compound consists essentially of two molecules of BHT.

 

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
375 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Read-across approach. Klimisch 2. No data on GLP.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Key study:

The analogue CAS No. 119-47-1 (6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol) which shares the same functional group (alkylphenol)

with the two main constituents of the substance Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol, also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 119-47-1 can be used for the read-across approach.

Based on experimental data, the read-across approach is applied and the NOAEL for maternal toxicity is 93.5 mg/kg bw/day and the NOAEL for developmental toxicity is 375 mg/kg bw/day (the highest dose tested).  


Justification for selection of Effect on developmental toxicity: via oral route:
Key study:Based on experimental data, the read-across approach is applied and the NOAEL for maternal toxicity is 93.5 mg/kg bw/day and the NOAEL for developmental toxicity is 375 mg/kg bw/day (the highest dose tested).

Justification for classification or non-classification

Based on the available data, the substance is not classified for toxicity to reproduction.