Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.941 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
70.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction: 12 / (0.380 * 0.3*(10 / 6.7)) = 10.579 mg/kg bw (0.380 m3/kg bw is the respiratory conversion factor in rats for 8 h; Factor 0.3 is a compensation for lower expected respiratory absorption as documented under the basic toxicokinetics assessment; factor 10/6.7 is a compensation for increased respiratory rate for workers).

AF for dose response relationship:
1
Justification:
ECHA/ default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable to inhalation exposure
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed.
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction: 12 / (1) = 12 mg/kg bw (No compensation for route: based on the basic toxicokinetics assessment, dermal absorption is considered to be equal to oral absorption = 100 %)

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed.
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

An OECD 422 combined repeat dose and reproductive/developmental toxicity screening test was performed in rats for o-sec-butylphenol (Japan Existing Chemical Data Base). With regard to repeat dose toxicity, no animals died in any groups. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, an ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females, and hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group. Concentration of total cholesterol was also increased in males given 300 mg/kg. No adverse effects were detected on food consumption and body weight change in males and females of the 300 mg/kg group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period. The NOELs for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females. Regarding reproductive and developmental toxicity, no adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups. NOELs for reproductive and developmental toxicity are considered to be 300 mg/kg/day in males, females and pups.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.232 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
34.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction: 12 / (1.150 * 0.3) = 5.217 mg/kg bw (1.150 m3/kg bw is the respiratory conversion factor in rats for 24 h; Factor 0.3 is a compensation for lower expected respiratory absorption as documented under the basic toxicokinetics assessment)

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable for inhalation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed.
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction: 12 / (1) = 12 mg/kg bw (No compensation for route: based on the basic toxicokinetics assessment, dermal absorption is considered to be equal to oral absorption = 100 %)

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed.
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.02 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
12 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction: 12 / (1) = 12 mg/kg bw (No comp. for route)

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
No indication that a factor for quality is needed.
AF for remaining uncertainties:
1
Justification:
No indication that a factor is needed.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
Explanation for the modification of the dose descriptor starting point:

Acute toxicity oral: LD50 in Sprague-Dawley strain rat > 200 - < 2000 mg/kg bodyweight (H301).

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

An OECD 422 combined repeat dose and reproductive/developmental toxicity screening test was performed in rats for o-sec-butylphenol (Japan Existing Chemical Data Base). With regard to repeat dose toxicity, no animals died in any groups. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, an ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females, and hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group. Concentration of total cholesterol was also increased in males given 300 mg/kg. No adverse effects were detected on food consumption and body weight change in males and females of the 300 mg/kg group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period. The NOELs for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females. Regarding reproductive and developmental toxicity, no adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups. NOELs for reproductive and developmental toxicity are considered to be 300 mg/kg/day in males, females and pups.