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

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated 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:

other: see 'Remark'

Remarks:

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.

Data source

Reference

Reference Type:

other: read-across

Title:

Unnamed

Year:

2010

Materials and methods

Principles of method if other than guideline:

Read-across from experimental data on an analogue.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol

EC Number:

204-327-1

EC Name:

6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol

Cas Number:

119-47-1

IUPAC Name:

2,2'-methylenebis(6-tert-butyl-4-methylphenol)

Details on test material:

- Molecular formula (if other than submission substance): C23H32O2
- Molecular weight (if other than submission substance): 340.5
- Smiles notation (if other than submission substance): c1(c(c(cc(c1)C)C(C)(C)C)O)Cc1c(c(cc(c1)C)C(C)(C)C)O
- InChl (if other than submission substance): InChI=1/C23H32O2/c1-14-9-16(20(24)18(11-14)22(3,4)5)13-17-10-15(2)12-19(21(17)25)23(6,7)8/h9-12,24-25H,13H2,1-8H3
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

93.5 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

375 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

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. There 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 6.25 for 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol) 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 0.02mg/L at 25 ºC for 6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol)

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

 

CAS Number		Source chemical 119-47-1	Target chemical
CHEMICAL NAME		6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol	Reaction mass of 2,6-di-tert-butylphenol and 2,4,6-tri-tert-butylphenol
PHYSICO-CHEMICAL DATA
Melting Point		Experimental results: 118-128 ºC	Experimental results: -36.3 ºC to -28.2 ºC
Boiling Point		No data	Experimental results: 253.9 ºC
pKa		No data	No data
Partition Coefficient (log Kow)		Experimental results: Log Pow = 6.25	Experimental results: log Pow = 4.9
Water solubility		Experimental results: 0.02mg/l at 25 ºC	Experimental results: 0.4 ± 0.3 mg/l at 20 ºC
Vapour pressure		Estimated data: 2.50E-09 mm Hg at 25 ºC	Experimental results: 310 Pa at 20 °C (2.33 mmHg)
ENVIRONMENTAL FATE and PATHWAY
Aerobic Biodegradation		Estimated and experimental data: Not readily biodegradable	Experimental results: Not readily biodegradable
ENVIRONMENTAL TOXICITY
Acute Toxicity to Fish		Estimated data: ECOSAR LC50 (96 h) =0.01mg/l	Experimental data: Key study: LC50 (96 h)=0.31mg/L
Acute Toxicity to Aquatic Invertebrates		Estimated data: ECOSAR EC50 (48 h) = 0.004 mg/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) = 0.856 mg/L (Chemical may not be soluble enough to measure this predicted effect).	Experimental data:  Key study: EC50(72h)=3mg/L NOEC=1.6 mg/L
MAMMALIAN TOXICITY
Acute Toxicity: Oral		Experimental data: Key study: LD50>5000 mg/kg bw (rats)	Experimental data: Key study: LD50 = 2976 mg/kg bw (rats)
Acute Toxicity: Dermal		No data	Experimental data: Key study: LD50 > 2000 mg/kg bw (rats)
Skin and eye irritation. Skin sensitisation.		No data	Experimental data: Key studies: Not a skin irritant.   Eye damage Category 1   Not a skin sensitizer.
Repeated Dose Toxicity		Experimental results: NOAEL from chronic study:12.7 mg/kg bw/day for male rats and 15.1 mg/kg bw/day for female rats	No data
Genetic Toxicity in vitro	Gene mutation in bacteria	No data	No data
	Chromosomal aberrations	No data	No data
	Gene mutation in mammalian cells	No data	No data
Genetic Toxicity in vivo		No data	No data
Carcinogenicity		No data	No data
Toxicity to reproduction		Experimental results:     Developmental toxicity: The NOAEL for maternal toxicity is 93.5 mg/kg bw/day and the NOAEL for developmental toxicity was 375 mg/kg bw/day (the highest dose tested).	Experimental results: Read-across from6,6'-di-tert-butyl-2,2'-methylenedi-p-cresol   Developmental toxicity: The NOAEL for maternal toxicity is 93.5 mg/kg bw/day and the NOAEL for developmental toxicity was 375 mg/kg bw/day (the highest dose tested).

 

Applicant's summary and conclusion

Conclusions:

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).

Executive summary:

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).