Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Modified dose descriptor starting point:
NOAEC
Value:
10 mg/m³
Explanation for the modification of the dose descriptor starting point:

Subchronic inhalation toxicity study for Bisphenol A

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Rationale for DNEL derivation Bisphenol A (see also REACH registration for Bisphenol A):

Inhalation (systemic and local, long-term) – based on SCOEL assessment for Bisphenol A (13 week inhalation study)

SCOEL/SUM/113 (June 2014: "The inhalation NOAEC of 10 mg/m3 is taken as the starting point for recommending an OEL. The critical effect in this study was respiratory tract irritation. This value of 10 is divided by an assessment factor of 3 to cover the uncertainties related to the inter-species extrapolation in these local effects resulting in a recommended OEL of 3 mg/m3. Using the preferred value approach, 3 mg/m3 is rounded to 2 mg/m3. There are also some concerns about long-term systemic effects (liver and kidney effects), which may not have been fully addressed in this subchronic inhalation study. There is a 17–25-fold safety margin to the inhalation exposure levels of 34 and 49 mg/m3, which correspond to the BMDL10 of ~ 3.5 mg/kg bw (EFSA 2014) and to the NOAEL of 5 mg/kg bw observed for kidney and liver effects in oral studies. Because liver and kidney effects observed in oral long-term rodent studies were very mild even at the highest dose levels (50 mg/kg bw and 500/600 mg/kg bw, Tyl et al 2002 and 2008), this margin of safety is considered sufficient to cover extrapolation to long-term exposure, and also to cover possible remaining inter- and intra-species differences in toxicokinetics and toxicodynamics."

Inhalation (systemic and local, acute) – based on SCOEL assessment for Bisphenol A (13 week inhalation study)

SCOEL/SUM/113 (June 2014: "The inhalation NOAEC of 10 mg/m3 is taken as the starting point for recommending an OEL. The critical effect in this study was respiratory tract irritation. This value of 10 is divided by an assessment factor of 3 to cover the uncertainties related to the inter-species extrapolation in these local effects resulting in a recommended OEL of 3 mg/m3. Using the preferred value approach, 3 mg/m3 is rounded to 2 mg/m3. ....There is no toxicological basis for recommending an additional specific short-term exposure limit (STEL).” As a conservative approach short-term and long-term DNEL will be set at the same value; 2 mg/m3.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Modified dose descriptor starting point:
NOAEC
Value:
10 mg/m³
Explanation for the modification of the dose descriptor starting point:

Subchronic inhalation toxicity study

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: following SCOEL Recommendation of 2014 for the main constituent Bisphenol A
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.008 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: following EFSA 2015 t-TDI (temporary-tolerable daily intake) definition for the main constituent Bisphenol A
Modified dose descriptor starting point:
other: human equivalent dose (HED)
Explanation for the modification of the dose descriptor starting point:

t-TDI defined by EFSA in 2015

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.008 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ollowing EFSA 2015 t-TDI (temporary-tolerable daily intake) definition for the main constituent Bisphenol A
Explanation for the modification of the dose descriptor starting point:

t-TDI defined by EFSA in 2015

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Rationale for DNEL derivation Bisphenol A (see also REACH registration for Bisphenol A, CAS-No. 80 -05 -7):

For explanation to inhalation and dermal exposure DNEL derivation Bisphenol A please see 'Additional Information - Workers'.

General Population oral (long-term and acute systemic) – based on EFSA Scientific Opinion of 2015 for Bisphenol A (multi-generation reproduction toxiciy studies in rats and mice)

EFSA reevaluated Bisphenol A and published a Scientific Opinion in 2015: “Bisphenol A was found to affect kidney and liver weight in parental animals and in all the generations of rats and mice examined in multi-generation studies. These effects were considered by EFSA (2006, 2010) as relevant systemic effects for the identification of a NOAEL. In mice the increased kidney weight was associated with nephropathy at the highest Bisphenol A dose. Liver weight was increased in rats (relative weight) and mice (both absolute and relative weight). The latter species also showed hepatocellular hypertrophy. The CEF Panel considered the endpoint “general toxicity” for hazard characterisation, using a reference point from the two-generation study in mice, which provided a BMDL10 for mean relative kidney weight of 8 960 μg/kg bw per day in male mice of the F0 generation.