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

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: read-across from several repeated dose toxicity studies, including chronic data

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 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.

Data source

Reference

Reference Type:

other: read-across

Title:

Unnamed

Year:

2010

Materials and methods

Principles of method if other than guideline:

Read-across approach from data on an analogue.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

204-881-4

EC Name:

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

Cas Number:

128-37-0

IUPAC Name:

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

Details on test material:

- Molecular formula (if other than submission substance): C15H24O
- Molecular weight (if other than submission substance): 220.35
- Smiles notation (if other than submission substance): Cc1cc(c(O)c(c1)C(C)(C)C)C(C)(C)C
- InChl (if other than submission substance): InChI=1/C15H24O/c1-10-8-11(14(2,3)4)13(16)12(9-10)15(5,6)7/h8-9,16H,1-7H3
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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.

  

- 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

Applicant's summary and conclusion

Conclusions:

Based on experimental data, the read-across approach is applied and the NOAEL is considered to be 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 is considered to be 25 mg/kg bw/day.